N-link hydroxamic acid derivatives useful as antibacterial agents

ABSTRACT

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections.

This application is a continuation application under 35 U.S.C. §120 ofU.S. patent application Ser. No. 13/515,607, filed on Dec. 6, 2012,which claims priority to PCT/IB2010/055596 filed Dec. 6, 2010, whichclaims priority to U.S. Provisional Patent Application No. 61/287,035filed Dec. 16, 2009, the disclosures of which are hereby incorporated byreference in its entirety.

FIELD OF THE INVENTION

This invention relates to novel hydroxamic acid derivatives that areuseful for the treatment of bacterial infections, especiallyGram-negative infections. The invention also relates to methods of usingsuch compounds in the treatment of bacterial infections in mammals, andto pharmaceutical compositions containing such compounds.

BACKGROUND OF THE INVENTION

Infection by Gram-negative bacteria such as Pseudomonas aeruginosa,Extended Spectrum β-lactamase producing (ESBL) Enterobacteriaceae, andAcinetobacter baumannii is a major health problem, especially in thecase of hospital-acquired infections. In addition, there is anincreasing level of resistance to current antibiotic therapies, whichseverely limits treatment options. For example, in 2002, 33% ofPseudomonas aeruginosa infections from intensive care units wereresistant to fluoroquinolones, while resistance to imipenem was 22% (CID42: 657-68, 2006). In addition, multi-drug resistant (MDR) infectionsare also increasing; in the case of Pseudomonas aeruginosa, MDRincreased from 4% in 1992 to 14% in 2002 (Biochem Pharm 71: 991, 2006).

Gram-negative bacteria are unique in that their outer membrane containslipopolysaccharide (LPS), which is crucial for maintaining membraneintegrity, and is essential for bacterial viability (reviewed in Ann.Rev. Biochem 76: 295-329, 2007). The major lipid component of LPS isLipid A, and inhibition of Lipid A biosynthesis is lethal to bacteria.Lipid A is synthesized on the cytoplasmic surface of the bacterial innermembrane via a pathway that consists of nine different enzymes. Theseenzymes are highly conserved in most gram-negative bacteria. LpxC is theenzyme that catalyzes the first committed step in the Lipid Abiosynthetic pathway, the removal of the N-acetyl group ofUDP-3-O—(R-3-hydroxymyristoyl)-N-acetylglucosamine. LpxC is aZn²⁺-dependent enzyme that has no mammalian homologue, making it a goodtarget for the development of novel antibiotics. Several inhibitors ofLpxC [UDP-3-O—(R-3-hydroxymyristoyl)-GlcNAc deacetylase]with low nMaffinity have been reported (Biochemistry 45: 7940-48, 2006).

SUMMARY OF THE INVENTION

A new class of LpxC inhibitors has been discovered. These compounds, ortheir pharmaceutical salts, can be represented by Formula I below:

in which:

-   R¹ is represented by C₁-C₃ alkyl;-   R² is represented by hydrogen or C₁-C₃ alkyl;-   R³ is represented by hydrogen, halogen, C₁-C₃alkyl, C₁-C₃alkoxy,    trifluoromethyl, or trifluoromethoxy;-   L is absent, or is represented by a moiety selected from the group    consisting of C₁-C₆ alkylene which may be optionally substituted,    C₂-C₆ alkenylene, C₂-C₆ alkynylene, —(CH₂)_(p)—O—(CH₂)_(n),-   —(CH₂)_(p)—O—(CH₂)_(z)—O—(CH₂)_(n)—;-   n is represented by an integer ranging from 0 to 4;-   p is represented by an integer ranging from 0 to 4;-   q is represented by an integer ranging from 0 to 6;-   z is represented by an integer ranging from 1 to 4;-   D is represented by a substituent selected from the group consisting    of:    -   i) (C₃-C₁₀)cycloalkyl, optionally substituted,    -   ii) (C₆-C₁₀)aryl, optionally substituted,    -   iii) heteroaryl, optionally substituted,    -   iv) heterocyclic, optionally substituted,-   T is absent, or is represented by —S—(CH₂)_(z)—O—(CH₂)_(n),    —O—(CH₂)—S—(CH₂)_(n), —(CH₂)_(q)—, —(CH₂)_(n)—C(O)—(CH₂)_(p)—,    —(CH₂)_(n)—O—(CH₂)_(p)—, —(CH₂)_(n)—S—(CH₂)_(p),    —O—(CH₂)_(p)—C(O)—(CH₂)_(n)—,    —(CH₂)_(p)—C(O)—(CH₂)_(q)—O—(CH₂)_(n)—, —O—(CH₂)_(z)—O—(CH₂)_(n)—,    —O—C₁-C₆ alkylene optionally substituted, —S—C₁-C₆ alkylene    optionally substituted, —O—(CH₂)_(z)—O—(CH₂)_(z)—O—(CH₂)_(n)—,    —S—(CH₂)_(z)—S—(CH₂)_(n)—,-   —(CH₂)_(n)—SH, or —(CH₂)_(n)—OH, and;-   G is absent, or is represented by a substituent selected from the    group consisting of:    -   i) (C₃-C₁₀)cycloalkyl, optionally substituted;    -   ii) (C₆-C₁₀)aryl optionally substituted;    -   iii) heteroaryl, optionally substituted, and;    -   iv) heterocyclic, optionally substituted.

The compounds of Formula I exhibit antibacterial activity, especiallyagainst Gram-negative organisms. They may be used to treat bacterialinfections in mammals, especially humans. The compounds may also be usedfor veterinary applications, such as treating infections in livestockand companion animals.

The compounds of Formula I are useful for treating a variety ofinfections; especially Gram-negative infections including nosocomialpneumonia, urinary tract infections, systemic infections (bacteremia andsepsis), skin and soft tissue infections, surgical infections,intraabdominal infections, lung infections (including those in patientswith cystic fibrosis), Helicobacter pylori (and relief of associatedgastric complications such as peptic ulcer disease, gastriccarcinogenesis, etc.), endocarditis, diabetic foot infections,osteomyelitis, and central nervous system infections.

In order to simplify administration, the compounds will typically beadmixed with at least one excipient and formulated into a pharmaceuticaldosage form. Examples of such dosage forms include tablets, capsules,solutions/suspensions for injection, aerosols for inhalation andsolutions/suspensions for oral ingestion.

DETAILED DESCRIPTION OF THE INVENTION

The headings within this document are only being utilized to expediteits review by the reader. They should not be construed as limiting theinvention or claims in any manner.

Definitions and Exemplification

As used throughout this application, including the claims, the followingterms have the meanings defined below, unless specifically indicatedotherwise. The plural and singular should be treated as interchangeable,other than the indication of number:

-   -   a. “C₁-C₃ alkyl” refers to a branched or straight chained alkyl        group containing from 1 to 3 carbon atoms, such as methyl,        ethyl, n-propyl, or isopropyl, etc.    -   b. “C₁-C₃ alkoxy” refers to a straight or branched chain alkoxy        group containing from 1 to 3 carbon atoms, such as methoxy,        ethoxy, n-propoxy, isopropoxy, etc.    -   c. “halogen” refers to a chlorine, fluorine, iodine, or bromine        atom.    -   d. “C₁-C₆ alkylene” refers to a branched or straight chained        alkyl group containing from 1 to 6 carbon atoms, having single        bonds for attachment to other groups at two different carbon        atoms. Examples of such alkylene groups include methylene,        ethylene, n-propylene, isopropylene, n-butylene, isobutylene,        pentylene, etc. This alkylene moiety may be optionally        substituted in which up to 6 hydrogen atoms are replaced by a        substituent selected from the group consisting of halogen,        cyano, sulfonamide, imino, iminohydroxy, iminoalkoxy,        iminoalkyl, —O—R^(a), —SR^(a), and —NR^(a)R^(b) in which R^(a)        and R^(b) are each independently represented by hydrogen or        C₁-C₆alkyl which may be optionally substituted.    -   e. “C₂-C₆ alkenylene” refers to a branched or straight chained        alkene group containing from 2 to 6 carbon atoms and having        single bonds for attachment to other groups at two different        carbon atoms. Examples of such groups include —CH₂—CH═CH—CH₂—,        —CH₂—CH═CH—CH═CH—, etc.    -   f. “C₂-C₆ alkynylene” refers to a branched or straight chained        alkyne group containing from 2 to 6 carbon atoms and having        single bonds for attachment to other groups at two different        carbon atoms. Examples of such groups include —CH₂—C≡C—CH₂—,        —CH₂—CH≡CH—CH≡CH—, etc.    -   g. “C₁-C₆ alkyl” refers to a branched or straight chained alkyl        group containing from 1 to 6 carbon atoms, such as methyl,        ethyl, n-propyl, isopropyl, n-butyl, isobutyl, pentyl, etc.    -   h. “C₁-C₆ alkyl, optionally substituted” refers to a branched or        straight chained alkyl group containing from 1 to 6 carbon        atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl,        isobutyl, pentyl, etc. Such an alkyl group may be optionally        substituted, in which up to 6 hydrogen atoms are replaced by a        substituent selected from the group consisting of halogen,        cyano, sulfonamide, imino, iminoalkoxy, iminohydroxy,        iminoalkyl, —O—R^(a), —SR^(a), and —NR^(a)R^(b) in which R^(a)        and R^(b) are each independently represented by hydrogen or        C₁-C₆lkyl which may be optionally substituted as described        above.    -   i. “C₁-C₆ alkoxy” refers to a straight or branched chain alkoxy        group containing from 1 to 6 carbon atoms, such as methoxy,        ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, pentoxy,        etc; which may be unsubstituted or optionally further        substituted with halogen, hydroxy, thiol or amino(—NH₂).    -   j. “(C₃-C₁₀)cycloalkyl” refers to a saturated or partially        saturated monocyclic, bicyclic, bridged bicyclic or tricyclic        alkyl radical wherein each cyclic moiety has 3 to 10 carbon        atoms. Examples of such cycloalkyl radicals include cyclopropyl,        cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, and the like.    -   k. “(C₃-C₁₀)cycloalkyl” optionally substituted refers to a        (C₃-C₁₀)cycloalkyl moiety as described above. Such a cycloalkyl        group may be optionally substituted, in which up to 4 hydrogen        atoms are replaced by a substituent selected from the group        consisting of halogen, cyano, nitro, hydroxy, (C₁-C₆)alkyl        optionally substituted, (C₁-C₆)alkoxy optionally substituted,        trifluoromethyl, trifluoromethoxy, phosphate, oxo, —SO₂NR⁴R⁵,        —(CH₂)_(m)—NR⁵—C(O)—R⁴, —(CH₂)_(m)—C(O)—N—R⁴R⁵, —C(O)—R⁴,        —C(O)—O—R⁴, —SR⁴, —SO₂R⁴and —NR⁴R⁵, in which R⁴ and R⁵ are each        independently represented by hydrogen or C₁-C₆ alkyl, which may        be optionally substituted as defined above, and m is 0-4. These        substituents may be the same or different and may be located at        any position of the ring, that is chemically permissible.    -   l. “(C₆-C₁₀)aryl” means a cyclic, aromatic hydrocarbon        containing from 6 to 10 carbon atoms. Examples of such aryl        groups include phenyl, naphthyl, etc.    -   m. “(C₆-C₁₀)aryl optionally substituted” means a cyclic,        aromatic hydrocarbon as defined above. Such an aryl moiety may        be optionally substituted with up to 4 non-hydrogen        substituents, each substituent is independently selected from        the group consisting of halogen, cyano, nitro, hydroxy,        (C₁-C₆)alkyl optionally substituted, (C₁-C₆)alkoxy optionally        substituted, trifluoromethyl, trifluoromethoxy, phosphate,        —SO₂NR⁴R⁵, —(CH₂)_(m)—NR⁵—C(O)—R⁴, —(CH₂)_(m)—C(O)—N—R⁴R⁵,        —C(O)—R⁴, —C(O)—O—R⁴, —SR⁴, —SO₂R⁴and —NR⁴R⁵, in which m, R⁴ and        R⁵ are as defined above. These substituents may be the same or        different and may be located at any position of the ring, that        is chemically permissible. “Phenyl optionally substituted”        refers to a phenyl ring substituted as described above.    -   n. “heteroaryl” refers to an aromatic ring having one, or more,        heteroatoms selected from oxygen, nitrogen and sulfur. More        specifically, it refers to a 5- or 6-membered ring containing 1,        2, 3, or 4 nitrogen atoms; 1 oxygen atom; 1 sulfur atom; 1        nitrogen and 1 sulfur atom; 1 nitrogen and 1 oxygen atom; 2        nitrogen atoms and 1 oxygen atom; or 2 nitrogen atoms and 1        sulfur atom. The 5-membered ring has 2 double bonds and the        6-membered ring has 3 double bonds. The term heteroaryl also        includes bicyclic groups in which the heteroaryl ring is fused        to a benzene ring, heterocyclic ring, a cycloalkyl ring, or        another heteroaryl ring. Examples of such heteroaryl ring        systems include, but are not limited to, pyrrolyl, furanyl,        thienyl, imidazolyl, oxazolyl, indolyl, thiazolyl, pyrazolyl,        pyridinyl, pyrimidinyl, purinyl, quinolinyl, benzofuran,        tetrazole, isoquinolinyl, oxadiazolyl, thiadiazolyl,        isothiazolyl, isoxazolyl, triazolyl, benzo[b]thienyl, 2-, 4-,        5-, 6-, or 7-benzoxazolyl, 7-benzimidazolyl, or benzothiazolyl.    -   o. “heteroaryl, optionally substituted,” refers to a heteroaryl        moiety as defined immediately above, in which up to 4 carbon        atoms of the heteroaryl moiety may be substituted with a        substituent, each substituent is independently selected from the        group consisting of halogen, cyano, nitro, hydroxy, (C₁-C₆)alkyl        optionally substituted, (C₁-C₆)alkoxy optionally substituted,        trifluoromethyl, trifluoromethoxy, phosphate, SO₂NR⁴R⁵,        —(CH₂)_(m)—N—C(O)—R⁴, —(CH₂)_(m)—C(O)—N—R⁴R⁵, —C(O)—R⁴,        —C(O)—O—R⁴, —SR⁴, —SO₂R⁴and —NR⁴R⁵, in which m, R⁴ and R⁵ are as        defined above. These substituents may be the same or different        and may be located at any position of the ring, that is        chemically permissible.    -   p. “heterocycle” or “heterocyclic ring” refers to any 3- or        4-membered ring containing a heteroatom selected from oxygen,        nitrogen and sulfur; or a 5-, 6-, 7-, 8-, 9-, or 10-membered        ring containing 1, 2, or 3 nitrogen atoms; 1 oxygen atom; 1        sulfur atom; 1 nitrogen and 1 sulfur atom; 1 nitrogen and 1        oxygen atom; 2 oxygen atoms in non-adjacent positions; 1 oxygen        and 1 sulfur atom in non-adjacent positions; or 2 sulfur atoms        in non-adjacent positions. The 5-membered ring has 0 to 1 double        bonds, the 6- and 7-membered rings have 0 to 2 double bonds, and        the 8, 9, or 10 membered rings may have 0, 1, 2, or 3 double        bonds. The term “heterocyclic” also includes bicyclic groups in        which any of the above heterocyclic rings is fused to a benzene        ring, a cyclohexane or cyclopentane ring or another heterocyclic        ring (for example, indolyl, quinolyl, isoquinolyl,        tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl or        benzothienyl and the like). Heterocyclics include: pyrrolidinyl,        tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl,        piperazinyl, azepane, azocane, morpholinyl, isochromyl,        quinolinyl, tetrahydrotriazine, tetrahydropyrazole,        dihydro-oxathiol-4-yl, dihydro-1H-isoindole,        tetrahydro-oxazolyl, tetrahydro-oxazinyl, thiomorpholinyl,        tetrahydropyrimidinyl, dioxolinyl, octahydrobenzofuranyl,        octahydrobenzimidazolyl, and octahydrobenzothiazolyl.    -   q. “heterocyclic, optionally substituted” refers to a        heterocyclic moiety as defined immediately above, in which up to        4 carbon atoms of the heterocycle moiety may be substituted with        a substituent, each substituent is independently selected from        the group consisting of halogen, cyano, nitro, hydroxy,        (C₁-C₆)alkyl optionally substituted, (C₁-C₆)alkoxy optionally        substituted, trifluoromethyl, trifluoromethoxy, phosphate, oxo,        SO₂NR⁴R⁵, —(CH₂)_(m)—N—C(O)—R⁴, —(CH₂)_(m)—C(O)—N—R⁴R⁵,        —C(O)—R⁴, —C(O)—O—R⁴, —SR⁴, —SO₂R⁴and —NR⁴R⁵, in which m, R⁴ and        R⁵ are as defined above. These substituents may be the same or        different and may be located at any position of the ring that is        chemically permissible. Any nitrogen atom within such a        heterocyclic ring may optionally be substituted with        (C₁-C₆)alkyl, or any other substituent listed above, if such a        substitution is chemically permissible. Any sulfur atom in the        ring may be further substituted with 1 or 2 oxygen atoms.    -   r. “therapeutically effective amount” refers to an amount of a        compound of Formula I that, when administered to a patient,        provides the desired effect; i.e., lessening in the severity of        the symptoms associated with a bacterial infection, decreasing        the number of bacteria in the affected tissue, and/or preventing        bacteria in the affected tissue from increasing in number.    -   s. “patient” refers to warm blooded animals such as, for        example, guinea pigs, mice, rats, gerbils, cats, rabbits, dogs,        monkeys, chimpanzees, and humans.    -   t. “treat” refers to the ability of the compounds to relieve,        alleviate or slow the progression of the patient's bacterial        infection (or condition) or any tissue damage associated with        the disease.    -   u. “pharmaceutically acceptable” indicates that the substance or        composition must be compatible chemically and/or        toxicologically, with the other ingredients comprising a        formulation, and/or the mammal being treated therewith.    -   v. “isomer” means “stereoisomer” and “geometric isomer” as        defined below.    -   w. “stereoisomer” means compounds that possess one or more        chiral centers and each center may exist in the R or S        configuration. Stereoisomers include all diastereomeric,        enantiomeric and epimeric forms as well as racemates and        mixtures thereof.    -   v. “geometric isomer” means compounds that may exist in cis,        trans, anti, entgegen (E), and zusammen (Z) forms as well as        mixtures thereof.    -   w. Compounds of “Formula I”, “formula I” and “compounds of the        invention” are being used interchangeably thru-out the        application and should be treated as synonyms.    -    The phrase “pharmaceutically acceptable salt(s)”, as used        herein, unless otherwise indicated, includes salts of acidic or        basic groups which may be present in the compounds of the        present invention. The compounds of the present invention that        are basic in nature are capable of forming a wide variety of        salts with various inorganic and organic acids. The acids that        may be used to prepare pharmaceutically acceptable acid addition        salts of such basic compounds are those that form non-toxic acid        addition salts, i.e., salts containing pharmacologically        acceptable anions, such as the hydrochloride, hydrobromide,        hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid        phosphate, isonicotinate, acetate, lactate, salicylate, citrate,        acid citrate, tartrate, pantothenate, bitartrate, ascorbate,        succinate, maleate, gentisinate, fumarate, gluconate,        glucuronate, saccharate, formate, benzoate, glutamate,        methanesulfonate, ethanesulfonate, benzenesulfonate,        p-toluenesulfonate and pamoate [i.e.,        1,1′-methylene-bis-(2-hydroxy-3-naphthoate)]salts. The compounds        of the present invention that include a basic moiety, such as an        amino group, may form pharmaceutically acceptable salts with        various amino acids, in addition to the acids mentioned above.        -   The invention also relates to base addition salts of the            compounds of the invention. The chemical bases that may be            used as reagents to prepare these pharmaceutically            acceptable base salts are those that form non-toxic base            salts with such compounds. Such non-toxic base salts            include, but are not limited to those derived from such            pharmacologically acceptable cations such as alkali metal            cations (e.g., potassium and sodium) and alkaline earth            metal cations (e.g., calcium and magnesium), ammonium or            water-soluble amine addition salts such as            N-methylglucamine-(meglumine), and the lower alkanolammonium            and other base salts of pharmaceutically acceptable organic            amines.        -   Suitable base salts are formed from bases which form            non-toxic salts. Non-limiting examples of suitable base            salts include the aluminum, arginine, benzathine, calcium,            choline, diethylamine, diolamine, glycine, lysine,            magnesium, meglumine, olamine, potassium, sodium,            tromethamine and zinc salts. Hemisalts of acids and bases            may also be formed, for example, hemisulphate and            hemicalcium salts.

For a review on suitable salts, see Handbook of Pharmaceutical Salts:Properties, Selection, and Use by Stahl and Wermuth (Wiley-VCH, 2002).Methods for making pharmaceutically acceptable salts of compounds of theinvention are known to one of skill in the art.

Certain of the compounds of the formula (I) may exist as geometricisomers. The compounds of the formula (I) may possess one or moreasymmetric centers, thus existing as two, or more, stereoisomeric forms.The present invention includes all the individual stereoisomers andgeometric isomers of the compounds of formula (I) and mixtures thereof.Individual enantiomers can be obtained by chiral separation or using therelevant enantiomer in the synthesis.

In addition, the compounds of the present invention can exist inunsolvated as well as solvated forms with pharmaceutically acceptablesolvents such as water, ethanol and the like. In general, the solvatedforms are considered equivalent to the unsolvated forms for the purposesof the present invention. The compounds may also exist in one or morecrystalline states, i.e. polymorphs, or they may exist as amorphoussolids. All such forms are encompassed by the claims.

The invention also relates to prodrugs of the compounds of theinvention. Thus certain derivatives of compounds of the invention whichmay have little or no pharmacological activity themselves can, whenadministered into or onto the body, be converted into compounds of theinvention having the desired activity, for example, by hydrolyticcleavage. Such derivatives are referred to as “prodrugs”. Furtherinformation on the use of prodrugs may be found in Pro-drugs as NovelDelivery Systems, Vol. 14, ACS Symposium Series (T. Higuchi and W.Stella) and Bioreversible Carriers in Drug Design, Pergamon Press, 1987(Ed. E. B. Roche, American Pharmaceutical Association).

This invention also encompasses compounds of the invention containingprotective groups. One skilled in the art will also appreciate thatcompounds of the invention can also be prepared with certain protectinggroups that are useful for purification or storage and can be removedbefore administration to a patient. The protection and deprotection offunctional groups is described in “Protective Groups in OrganicChemistry”, edited by J. W. F. McOmie, Plenum Press (1973) and“Protective Groups in Organic Synthesis”, 3rd edition, T. W. Greene andP. G. M. Wuts, Wiley-Interscience (1999).

The present invention also includes isotopically-labeled compounds,which are identical to those recited in formula I, but for the fact thatone or more atoms are replaced by an atom having an atomic mass or massnumber different from the atomic mass or mass number usually found innature. Examples of isotopes that can be incorporated into compounds ofthe invention include isotopes of hydrogen, carbon, nitrogen, oxygen,phosphorous, fluorine and chlorine, such as, but not limited to, ²H, ³H,¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O, ³¹P, ³²P, ³⁵S, ¹⁸F, and ³⁶Cl, respectively.Compounds of the present invention, prodrugs thereof, andpharmaceutically acceptable salts of said compounds or of said prodrugswhich contain the aforementioned isotopes and/or other isotopes of otheratoms are within the scope of this invention. Certainisotopically-labeled compounds of the present invention, for examplethose into which radioactive isotopes such as ³H and ¹⁴C areincorporated, are useful in drug and/or substrate tissue distributionassays. Tritiated, i.e., ³H, and carbon-14, i.e., ¹⁴C, isotopes areparticularly preferred for their ease of preparation and detectability.Further, substitution with heavier isotopes such as deuterium, i.e., ²H,can afford certain therapeutic advantages resulting from greatermetabolic stability, for example increased in vivo half-life or reduceddosage requirements and, hence, may be preferred in some circumstances.Isotopically-labeled compounds of this invention and prodrugs thereofcan generally be prepared by carrying out the procedures disclosed inthe Schemes and/or in the Examples below, by substituting a readilyavailable isotopically-labeled reagent for a non-isotopically-labeledreagent.

All of the compounds of Formula I contain a sulfonyl moiety as depictedbelow:

This sulfonyl moiety will always be substituted with a lower alkymoiety. Typically it will be methyl. The carbon atom adjacent to thesulfonyl may optionally be substituted, as represented by R². Typicallyboth R¹ and R² will be methyl.

As is readily apparent to one skilled in the art, the carbon adjacent tothe sulfonyl moiety is a chiral center. Therefore the compounds canexist as the racemate, as the S enantiomer, or as the R enantiomer. In afurther embodiment, the compounds may be prepared and administered asthe R-enantiomer, as depicted below:

As is readily apparent to one skilled in the art, the compound assynthesized will rarely be present exclusively as a single enantiomer.The opposite enantiomer (i.e. the S-enantiomer) may be present in minoramounts (i.e. “substantially pure”). This minor amount can be up to 10w/w %, more typically no greater than 5 w/w % and in a furtherembodiment no greater than 1 w/w %.

All of the compounds of Formula I contain a pyridinone as depictedbelow:

This pyridinone ring will be connected to the rest of the molecule viathe 1- and 4-positions as depicted above. The pyridinone moiety may beoptionally substituted, as depicted by the R³ moiety. R³ may representone non-hydrogen substituent, as defined above. This non-hydrogensubstituent may be located at any of positions 3, 4 or 5 of thepyridinone ring. Typically R³ will represent hydrogen.

While the presence of L, T and G are optional, all of the compounds ofFormula I will contain one of the substituents as defined by D. D may beany of aryl, cycloalkyl, heteroaryl or heterocyclic, as defined above.These ring systems may also be optionally substituted, as defined above.Any chemically permissible position of D may be bonded to the 4-positionof the pyridine ring or D may be connected to the pyridinone via thelinker as defined by L.

The molecule may contain one of the substituents defined by G. G, ifpresent, may be bonded directly to D. Alternatively, the linker T mayconnect G and D. G may be any of aryl, cycloalkyl, heteroaryl orheterocyclic as defined above. These ring systems may also be optionallysubstituted, as defined above.

If G is absent, the molecule may terminate with either T or D as thetail. If the molecule terminates with T, then one skilled in the artwill recognize that any of the linkers specified above will have anadditional hydrogen atom on the terminal atom of that specificsubstituent, due to the lack of a bond to G.

More specific embodiments of the invention include compounds of FormulaI in which:

-   -   a) R¹ is methyl;    -   b) R¹ and R² are each methyl;    -   c) R³ is hydrogen;    -   d) L is absent;    -   e) the compound is present as the R-enantiomer (i.e.        substantially pure);    -   f) R¹ and R² are each methyl, D is represented by optionally        substituted phenyl and the compound is present as the        R-enantiomer (i.e. substantially pure);    -   g) R¹ and R² are each methyl, L, G and T are all absent, D is        represented by optionally substituted phenyl, and the compound        is present as the R-enantiomer (i.e. substantially pure);    -   h) R¹ and R² are each methyl, L is absent, D is represented by        phenyl optionally substituted, T is absent, G is represented by        heteroaryl, optionally substituted and the compound is present        as the R-enantiomer (i.e. substantially pure).

In a further embodiment, the invention is directed to a subgenusrepresented by formula Ia below. As depicted below, L, T and G are allabsent. D is phenyl optionally substituted, R³ is hydrogen and thecompound is present as the R-enantiomer (i.e. the S-enantiomer mayoptionally be present as a minor impurity, typically no more than 5 w/w%, more typically no more than 1 w/w %). In a further embodiment, thephenyl ring is substituted with up to 3 substituents selected from thegroup consisting of halogen, hydroxy, C₁-C₃ alkyl, C₁-C₃ alkoxy,trifluoromethyl, trifluoromethoxy, and C₁-C₃ alkyl, optionallysubstituted with hydroxy or halogen.

In a further embodiment, the invention is directed to a subgenusrepresented by formula Ib below As depicted, L and T are both absent, Dis phenyl bonded directly to G which is optionally substitutedheteroaryl. R³ is hydrogen and the compound is present as theR-enantiomer (i.e. the S-enantiomer may optionally be present as a minorimpurity, typically no more than 5 w/w %, more typically no more than 1w/w %).

Synthesis

The compounds of Formula I can be prepared by a variety of methods thatare analogously known in the art. The reaction schemes presented belowillustrate one method for preparing these compounds. Others, includingmodifications thereof, will be readily apparent to one skilled in theart.

Scheme A below illustrates how to prepare the compounds of Formula I.The initial step in the synthesis, as depicted in Step A, is to conductan N-alkylation reaction between the pyridinone of structure 1 and thesulfonyl derivative of structure 2, generating the sulfonyl-pyridinonederivative of structure 3. In Step B, which is further illustrated inScheme B, the terminal carboxylate of structure 3 is converted to ahydroxamic acid derivative as is depicted in structure 4. In Step C,which is further illustrated in Scheme C, the terminal moiety, L-D-T-G,is attached to the 4-position of the pyridinone moiety, generating thedesired compound of Formula I.

As is readily apparent to one skilled in the art, the order in whichStep B and Step C are carried out is not critical. If desired, theterminal moiety represented by L-D-T-G may be attached to the pyridinoneand then the hydroxamic moiety may be incorporated into the molecule.Likewise, the synthetic team may partially complete either Step B orStep C and return to this portion of the molecule after completing themodifications required at the other end of the molecule. Such varationsare readily apparent to one of skilled in the art.

The N-alkylation depicted above in Step A can be carried out usingtechniques well known to medicinal chemists. One of the startingmaterials is the 2-pyridinone derivative of structure 1. In thispyridinone, R³ should be represented by the same moiety as is desired inthe final product, or a protected variation thereof. Many of thesepyridinone derivatives are known in the art and the remainder can beproduced using synthetic techniques analgously known in the art. Thereader's attention is directed to Tet. Lett. (2005) Vol 46, 7917 for adescription of such techniques. Preparation 2A infra, also illustratestheir preparation.

The other reactant is the protected alkyl sulfonate of structure 2. R¹and R² should both be represented by the same moiety as is desired inthe final product. An ethyl protecting group is depicted, but anystandard protecting group may be substituted. These alkyl sulfonates arealso known in the art. The reader's attention is directed to JOC, (1980)Vol 45, 8, 1486-89 for a description of their preparation. Preparation1A infra, also illustrates their preparation.

The N-alkylation can be carried out as is known in the art. Typicallyequivalent amounts of the compounds of structure 1 and 2 are contactedin an aprotic solvent such as tetrahydrofuran in the presence of a weakbase such as potassium carbonate, cesium carbonate, sodium carbonate,etc. The reactants are typically heated and the reaction is continueduntil completed. The desired product of structure 3 can be recovered andisolated as is known in the art. If desired, it can be purified, oralternatively the crude can be used in the next step of the reaction.

Scheme B illustrates how to incorporate the hydroxamic acid moiety intothe molecules. As is depicted in Step 1, the protecting group is removedfrom the carboxylic acid, thereby generating the intermediate ofstructure 3′. The manner in which this is accomplished will vary withthe identity of the actual protecting group and is well known to thoseskilled in the art.

In Step 2, the hydroxamic acid moiety, as depicted, is incorporated intothe molecule. This can also be carried out as is known in the art. Ifdesired, a protected hydroxylamine may be used, followed by a subsequentdeprotection reaction. Alternatively hydroxylamine may be directlyincorporated. In either case the hydroxamic acid functionality isincorporated into the molecule using standard amidation reactions. Forexample, the compound of structure 3′ may be contacted with an excess ofoxalyl chloride, in an aprotic solvent such as dichloromethane to allowformation of the corresponding acid chloride, followed by the additionof an excess of either the hydroxylamine or protected hydroxylamine. Thereaction is then allowed to proceed to completion and the compound ofstructure 4 or its corresponding protected intermediate is isolated fromthe reaction medium and purified as is known in the art. As mentionedabove, any deprotection, if required, may be carried out as is known inthe art. Alternatively the amide can be formed using the amide couplingreagent, 1,1′-carbonyliimidazole or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) (“EDCI”), as is known in the art.

In Scheme C, as shown above, the tail of the molecule, i.e L-D-T-G, isattached to the 4-position of the N-hydroxylated pyridinone intermediategenerated in Step B. The coupling reaction depicted in Scheme C can becarried out by two alternative methods.

In Option A, the halide function at the 4-position is directly displacedby the desired tail group. In Option B, the halide moiety is convertedto a boronate ester which is subsequently displaced by the desired tailgroup. Either strategy may be utilized.

If Option B is chosen, the boronation can be carried out usingtechniques well known to those skilled in the art. For example, theintermediate of structure 4 is placed in an aprotic solvent (such astetrahydrofuran or dioxane) and then contacted with an organobornane(such as neopentyl diboron, bis(pinolacto)diborane, etc.) in thepresence of both a transition metal catalyst (i.e. palladium) and a base(potassium acetate, cesium carbonate, etc.). The reaction is allowed toproceed to completion. The borylated intermediate describe by structure4′ may be isolated and purified as is known in the art, or the crude maybe used directly in the next step of the reaction.

Regardless of whether Option A or Option B is chosen, a couplingreaction is ultimately carried out to attach the terminal moiety,G-T-D-L, to the 4-position of the pyridinone intermediate. In Scheme Cabove, the co-reactant is depicted as G-T-D-L-M¹. However the reader isreminded that the presence of G, T, and L are all optional. Only D isrequired. Thus, the co-reactant with the pyridinone may be any of D-M¹,T-D-M¹, G-T-D-M¹, G-T-D-L-M¹, T-D-L-M¹ or D-L-M¹. Therefore, G-T-D-L-M¹will be represented by the same moiety as desired in the final product,except that it will be substituted by a halogen atom, a metal such asmagnesium, copper, or a boronate ester, etc. at the desired point ofattachment to the pyridinone intermediate (i.e. the other reactant). Thetails encompassed by Formula I, i.e. G-T-D-L, are either known in theart or can be prepared by methods analogously known in the art.

The manner in which the coupling reaction is carried out varies with thetype of bond being formed, i.e. (carbon-carbon, carbon-nitrogen,carbon-oxygen, carbon-sulfur, etc.). If a carbon-carbon bond is desired,then a Suzuki-Miyaura strategy may be used. In such a reaction M¹ willbe represented by a boronic acid/ester or a halogen atom. Equivalentmolar amounts of the reactants will be contacted in a solvent such asTHF, dioxane, water, toluene, or an admixture thereof; in the presenceof a transition metal catalyst such as palladium, or nickel (or resinbound catalyst) along with a base such as sodium carbonate, potassiumcarbonate, cesium fluoride or cesium carbonate. The reactants will beheated by microwave or other conventional technique till completed. Oncecompleted the desired product may be isolated and recovered from thereaction and further purified as is known in the art.

Alternatively an Ullmann coupling strategy may be used. In such areaction, M¹ will be copper or nickel and the 4-position of thepyridinone will be substituted with an iodine atom (i.e. Option A willbe chosen). Equivalent amounts of the reactants will be contacted in anaprotic solvent such as ether, DMF, or DME and the reactants are heatedtill the reaction is completed. The desired product of formula I may beisolated and purified as is known in the art.

If a carbon-oxygen or carbon-sulfur linkage is desired, then aWillamson/Ullmann ether coupling or Mitsunobu reaction may be utilizedto produce these derivatives. G-T-D-L-M¹ will be represented by the samemoiety as desired in the final product, except that it will besubstituted by a hydroxyl function at the desired point of attachment tothe pyridinone. If a thioether is desired, G-T-D-L-M² will be anappropriately substituted disulfide moiety.

The Ullmann ether reaction can be carried out in the presence of coppersalts. If a Williamson ether approach is used, then equivalent amountsof the reactants will be contacted in an aprotic solvent such as dioxanein the presence or absence of a phase transfer catalyst such as18-crown-6. A base such as potassium hydroxide, sodium t-butoxide orsodium methoxide will typically be added as well. The reactants will beheated by microwave or other conventional technique to reactioncompletion. The desired product may be isolated and purified as is knownin the art.

If a carbon-nitrogen bond is desired, then a Buchwald-Hartwigcross-coupling or Ullmann strategy, similar to that described above, maybe utilized. Equivalent amounts of the reactants will be contacted in anaprotic solvent such as ether, dimethylformamide, or dimethyoxyethane inthe presence of a source of copper, such as copper acetate, and a basesuch as pyridine or catalyst such as a palladium complex. The reactionwill be allowed to proceed to completion and the desired product may beisolated and purified as is known in the art.

The reaction schemes depicted above for producing the compound ofFormula I, are merely illustrative. As is readily apparent to oneskilled in the art, they may be modified depending upon the specificcompound, availability of reagents, etc.

Medical and Veterinary Uses

The compounds may be used for the treatment or prevention of infectiousdisorders, especially those caused by susceptible and multi-drugresistant (MDR) Gram-negative bacteria. Examples of such Gram-negativebacteria include Acinetobacter baumannii, Acinetobacter spp.,Achromobacter spp., Aeromonas spp., Bacteroides fragilis, Bordetellaspp., Borrelia spp., Brucella spp., Campylobacter spp., Citrobacterdiversus (koseri), Citrobacter freundii, Enterobacter aerogenes,Enterobacter cloacae, Escherichia coli, Francisella tularensis,Fusobacterium spp., Haemophilus influenzae (β-lactamase positive andnegative), Helicobacter pylori, Klebsiella oxytoca, Klebsiellapneumoniae (including those encoding extended-spectrum β-lactamases(hereinafter “ESBLs”), Legionella pneumophila, Moraxella catarrhalis(β-lactamase positive and negative), Morganella morganii, Neisseriagonorrhoeae, Neisseria meningitidis, Proteus vulgaris, Porphyromonasspp., Prevotella spp., members of the Enterobacteriaceae that expressESBLs KPCs, CTX-M, metallo-1-lactamases, and AmpC-type beta-lactamasesthat confer resistance to currently available cephalosporins,cephamycins, carbapenems, and beta-lactam/beta-lactamase inhibitorcombinations, Mannheimia haemolyticus, Pasteurella spp., Proteusmirabilis, Providencia spp., Pseudomonas aeruginosa, Pseudomonas spp.,Salmonella spp., Shigella spp., Serratia marcescens, Treponema spp.,Burkholderia cepacia, Vibrio spp., Yersinia spp., and Stenotrophomonasmalophilia.

In a more specific embodiment, the Gram-negative bacteria are selectedfrom the group consisting of Acinetobacter baumannii, Acinetobacterspp., Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli,Klebsiella oxytoca, Klebsiella pneumoniae, Serratia marcescens,Pseudomonas aeruginosa and members of the Enterobacteriaceae andPseudomonas that express ESBLs, KPCs, CTX-M, metallo-3-lactamases, andAmpC-type beta-lactamases that confer resistance to currently availablecephalosporins, cephamycins, carbapenems, and beta-lactam/beta-lactamaseinhibitor combinations.

Examples of infections that may be treated with the compounds of FormulaI include nosocomial pneumonia, urinary tract infections, systemicinfections (bacteremia and sepsis), skin and soft tissue infections,surgical infections, intraabdominal infections, lung infections inpatients with cystic fibrosis, patients suffering from lung infections,endocarditis, diabetic foot infections, osteomyelitis, and centralnervous system infections.

In addition, the compounds can be used to treat Helicobacter pyloriinfections in the GI tract of humans (and other mammals). Elimination ofthese bacteria is associated with improved health outcomes includingfewer dyspeptic symptoms, reduced peptic ulcer recurrence andrebleeding, reduced risk of gastric cancer, etc. A more detaileddiscussion of eradicating H. pylori and its impact on gastrointestinalillness may be found at: www.informahealthcare.com, Expert Opin. DrugSaf. (2008) 7(3).

In order to exhibit this anti-infective activity, the compounds need tobe administered in a therapeutically effective amount. A“therapeutically effective amount” is meant to describe a sufficientquantity of the compound to treat the infection, at a reasonablebenefit/risk ratio applicable to any such medical treatment. It will beunderstood, however, that the attending physician, within the scope ofsound medical judgment, will decide the total daily dosage of thecompound. The specific therapeutically effective dose level for anyparticular patient will depend upon a variety of factors including thedisorder being treated and the severity of the disorder; the activity ofthe specific compound employed; the specific composition employed; theage, body weight, general health, sex and diet of the patient; the timeof administration, route of administration, and rate of excretion of thespecific compound employed; the duration of the treatment; drugs used incombination or coincidental with the specific compound employed; andlike factors well known in the medical arts. As a general guidelinehowever, the total daily dose will typically range from about 0.1mg/kg/day to about 5000 mg/kg/day in single or in divided doses.Typically, dosages for humans will range from about 10 mg to about 3000mg per day, in a single or multiple doses.

Any route typically used to treat infectious illnesses, including oral,parenteral, topical, rectal, transmucosal, and intestinal, can be usedto administer the compounds. Parenteral administrations includeinjections to generate a systemic effect or injections directly into tothe afflicted area. Examples of parenteral administrations aresubcutaneous, intravenous, intramuscular, intradermal, intrathecal, andintraocular, intranasal, intravetricular injections or infusionstechniques. Topical administrations include the treatment of areasreadily accessibly by local application, such as, for example, eyes,ears including external and middle ear infections, vaginal, open wound,skin including the surface skin and the underneath dermal structures, orother lower intestinal tract. Transmucosal administration includes nasalaerosol or inhalation applications.

Formulations

Compounds of the invention can be formulated for administration in anyway for use in human or veterinary medicine, by analogy with otherbioactive agents such as antibiotics. Such methods are known in the artand are summarized below.

The composition can be formulated for administration by any route knownin the art, such as subdermal, by-inhalation, oral, topical orparenteral. The compositions may be in any form known in the art,including but not limited to tablets, capsules, powders, granules,lozenges, creams or liquid preparations, such as oral or sterileparenteral solutions or suspensions.

The topical formulations of the present invention can be presented as,for instance, ointments, creams or lotions, ophthalmic ointments/dropsand otic drops, impregnated dressings and aerosols, and may containappropriate conventional additives such as preservatives, solvents toassist drug penetration and emollients, etc. Such topical formulationsmay also contain conventional carriers, such as cream or ointment basesand ethanol or oleyl alcohol for lotions. Such carriers may be present,for example, from about 1% up to about 98% of the formulation.

Tablets and capsules for oral administration may be in unit dosepresentation form, and may contain conventional excipients such asbinding agents, for example acacia, gelatin, sorbitol, tragacanth, orpolyvinylpyrollidone; fillers, for example lactose, sugar, maize-starch,calcium phosphate, sorbitol or glycine; tabletting lubricants, forexample magnesium stearate, talc, polyethylene glycol or silica;disintegrants, for example potato starch; or acceptable wetting agentssuch as sodium lauryl sulphate. The tablets may be coated according tomethods will known in normal pharmaceutical practice.

Oral liquid preparations may be in the form of, for example, aqueous oroily suspensions, solutions, emulsions, syrups or elixirs, or may bepresented as a dry product for reconstitution with water or othersuitable vehicle before use. Such liquid preparations may containconventional additives, such as suspending agents, for example sorbitol,methyl cellulose, glucose syrup, gelatin, hydroxyethyl cellulose,carboxymethyl cellulose, aluminium stearate gel or hydrogenated ediblefats, emulsifying agents, for example lecithin, sorbitan monooleate, oracacia; non-aqueous vehicles (which may include edible oils), forexample almond oil, oily esters such as glycerin, propylene glycol, orethyl alcohol; preservatives, for example methyl or propylp-hydroxybenzoate or sorbic acid, and, if desired, conventionalflavoring or coloring agents.

For parenteral administration, fluid unit dosage forms are preparedutilizing the compound and a sterile vehicle, water being typical. Thecompound, depending on the vehicle and concentration used, can be eithersuspended or dissolved in the vehicle or other suitable solvent. Inpreparing solutions, the compound can be dissolved in water forinjection and filter sterilized before filling into a suitable vial orampoule and sealing. Advantageously, agents such as a local anestheticpreservative and buffering agents can be dissolved in the vehicle. Toenhance the stability, the composition can be frozen after filling intothe vial and the water removed under vacuum. The dry lyophilized powderis then sealed in the vial and an accompanying vial of water forinjection may be supplied to reconstitute the liquid prior to use.Parenteral suspensions are prepared in substantially the same mannerexcept that the compound is suspended in the vehicle instead of beingdissolved and sterilization cannot be accomplished by filtration. Thecompound can be sterilized by exposure to ethylene oxide beforesuspending in the sterile vehicle. Advantageously, a surfactant orwetting agent is included in the composition to facilitate uniformdistribution of the compound.

The compositions may contain, for example, from about 0.1% by weight, toabout 60% by weight, of the active material, depending on the method ofadministration. Where the compositions comprise dosage units, each unitwill contain, for example, from about 5-500 mg of the active ingredient.The dosage as employed for adult human treatment will range, forexample, from about 10 to 3000 mg per day, depending on the route andfrequency of administration.

If desired, the compounds of the invention may be administered incombination with one or more additional anti-bacterial agents (“theadditional active agent”). Such use of compounds of the invention incombination with an additional active agent may be for simultaneous,separate or sequential use.

The examples and preparations provided below further illustrate andexemplify the compounds of the present invention and methods ofpreparing such compounds. It is to be understood that the scope of thepresent invention is not limited in any way by the scope of thefollowing examples and preparations. In the following examples moleculeswith a single chiral center, unless otherwise noted, exist as a racemicmixture. Those molecules with two or more chiral centers, unlessotherwise noted, exist as a racemic mixture of diastereomers. Singleenantiomers/diastereomers may be obtained by methods known to thoseskilled in the art.

EXAMPLES Experimental Procedures

Experiments were generally carried out under an inert atmosphere(nitrogen or argon), particularly in cases where oxygen- ormoisture-sensitive reagents or intermediates were employed. Commercialsolvents and reagents were generally used without further purification,including anhydrous solvents where appropriate (generally Sure-Seal™products from the Aldrich Chemical Company, Milwaukee, Wis.). Massspectrometry data is reported from either liquid chromatography-massspectrometry (LCMS) or atmospheric pressure chemical ionization (APCI).Chemical shifts for nuclear magnetic resonance (NMR) data are expressedin parts per million (ppm, δ) referenced to residual peaks from thedeuterated solvents employed. Melting points are uncorrected. LowResolution Mass Spectra (LRMS) were recorded on either a Hewlett Packard5989®, utilizing chemical ionization (ammonium), or a Fisons (or MicroMass) Atmospheric Pressure Chemical Ionization (APCI) platform whichuses a 50/50 mixture of acetonitrile/water with 0.1% formic acid as theionizing agent. Room or ambient temperature refers to 20-25° C.

For syntheses referencing procedures in other Examples, reactionconditions (length of reaction and temperature) may vary. In general,reactions were followed by thin layer chromatography or massspectrometry, and subjected to work-up when appropriate. Purificationsmay vary between experiments: in general, solvents and the solventratios used for eluants/gradients were chosen to provide appropriateR_(f)s or retention times.

In the discussion above and in the examples below, the followingabbreviations have the following meanings. If an abbreviation is notdefined, it has its generally accepted meaning.

-   -   Aq.=aqueous    -   bm=broad multiplet    -   BOC=tert-butoxycarbonyl    -   bd=broad doublet    -   bs=broad singlet    -   CDI=1,1′-carbonyldiimidazole    -   d=doublet    -   dd=doublet of doublets    -   dq=doublet of quartets    -   dt=doublet of triplets    -   DIAD=diisopropyl azocarboxylate    -   DMF=dimethylformamide    -   DMA=dimethylacetamide    -   DMAP=dimethylaminopyridine    -   DMSO=dimethyl sulfoxide    -   eq.=equivalents    -   g=grams    -   h=hours    -   HPLC=high pressure liquid chromatography    -   LG=leaving group    -   m=multiplet    -   M=molar    -   M %=mole percent    -   max=maximum    -   meq=milliequivalent    -   mg=milligram    -   mL=milliliter    -   mm=millimeter    -   mmol=millimol    -   q=quartet    -   s=singlet    -   t or tr=triplet    -   TBS=tert-butyldimethylsilyl    -   TFA=trifluoroacetic acid    -   THF=tetrahydrofuran    -   TLC=thin layer chromatography    -   p-TLC=preparative thin layer chromatography    -   μL=microliter    -   N=normality    -   MeOH=methanol    -   DCM=dichloromethane    -   HCl=hydrochloric acid    -   ACN=acetonitrile    -   MS=mass spectrometry    -   rt=room temperature    -   EtOAc=ethyl acetate    -   EtO=ethoxy    -   Ac=acetate    -   NMP=1-methyl-2-pyrrolidinone    -   μL=microliter    -   J=coupling constant    -   NMR=nuclear magnetic resonance    -   MHz=megahertz    -   Hz=hertz    -   m/z=mass to charge ratio    -   min=minutes    -   ppt=precipitate    -   CBZ=benzyloxycarbonyl    -   DCC=1,3-dicyclohexylcarbodiimide    -   PyBop=benzotriazole-1-yl-oxy-trispyrrolidinophosphonium        hexafluorophosphate    -   Pd(dppf)Cl₂=bis(diphenylphosphino)ferrocenepalladium(II)        chloride Pd(dppf)Cl₂ DCM complex    -   Pd tetrakis=Tetrakis(triphenylphosphine)palladium(0)    -   Pd(II)EnCat=Pd(II) EnCat™BINAP 30    -   LDA=lithium diisopropylamide    -   mCPBA=meta-chloroperbenzoic acid    -   MTBE=methyl tert butyl ether    -   CDMT=2-chloro-4,6-dimethoxy-1,3,5-triazine    -   NMM=N-methyl morphiline    -   TMS=trimethyl silyl    -   TPP=triphenyl phosphine    -   TPPO=triphenyl phosphine oxide    -   DME=dimethyl ether    -   IPA=isopropanol    -   Et₂O=diethyl ether    -   LiHMDS=lithium hexamethyldisilazide/lithium        bis(trimethylsilyl)amide    -   9-BBN=9-Borabicyclo[3.3.1]nonane    -   sat.=saturated    -   MeTHF=2-methyltetrahydrofuran

Preparation of Starting Materials Preparation 1 Preparation 1A(+/−)-Ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate and IndividualEnantiomers (R) and (S) Step A) Ethyl 2-(methylsulfonyl)propanoate

Sodium methyl sulfinate (103 g, 937 mmol) was combined with the ethyl2-chloropropionate (109 g, 892 mmol) in ethanol (350 mL) in a 500 mL oneneck round bottom flask. The reaction was warmed to 77° C. for 20 hours,and then allowed to cool to room temperature. Solids were removed byfiltration through celite, and the filter pad was washed with ethanoland the combined filtrates were concentrated in vacuo. The crude productwas suspended in diethyl ether (250 mL), and solids were removed byfiltration. The filtrate was concentrated in vacuo to afford the titlecompound as a pale yellow oil (51 g, 73%). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.32 (t, J=7.05 Hz, 3 H) 1.67 (d, J=7.47 Hz, 3 H)3.05 (s, 3 H) 3.83-3.92 (m, 1 H) 4.18-4.37 (m, 2 H).

Step B) (+/−)-Ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate

Sodium hydride (60% dispersion in mineral oil, 2.33 g, 58.3 mmol) waswashed with hexane (2×10 mL) in a 100 mL two neck round bottom flaskunder nitrogen then suspended in DMF (30 mL). The suspension was treateddropwise with ethyl 2-(methylsulfonyl)propanoate (10.0 g, 55.49 mmol) inDMF (10 mL). The mixture was stirred 30 min at RT, cooled to 0° C., andtreated dropwise with 1,2-dibromoethane (5.17 mL, 58.8). The mixture wasallowed to warm to room temperature while stirring overnight. Themixture was quenched with saturated ammonium chloride (100 mL) and themixture was extracted with diethyl ether (4×50 mL). Combined organicswere washed with 50% saturated sodium chloride (4×50 mL), dried (MgSO₄),filtered and the filtrate concentrated in vacuo. Crude material waschromatographed over silica gel (350 g, 230-400 mesh) eluting with10-20% EtOAc/hexane to afford the title compound as a pale yellow oil(7.9 g, 50%). ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.33 (t, J=7.05 Hz, 3H) 1.64 (s, 3 H) 2.49-2.59 (m, 1 H) 2.78 (ddd, J=13.89, 10.16, 6.64 Hz,1 H) 3.05 (s, 3 H) 3.33-3.41 (m, 1 H) 3.46-3.54 (m, 1 H) 4.22-4.37 (m, 2H).

Step C) Chiral Separation of (+/−)-Ethyl4-bromo-2-methyl-2-(methylsulfonyl)butanoate

Crude (+/−)-ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate (1.82 kg)was purified via flash chromatography using an LP-600 column and tolueneas the eluant to afford pure (+/−)-ethyl4-bromo-2-methyl-2-(methylsulfonyl)butanoate (1.63 kg). The purifiedmaterial was dissolved in ethanol (75 g/L) and resolved via chiralmulti-column chromatography (condition listed in Table 1) on MCC-2 toafford enantiomer 1 (738.4 g, rt=4.719 min, [α]₅₈₉ ²⁰=+14.10) at 99%enantiomeric purity and enantiomer #2 (763.8 g, rt=4.040 min) at 95%enantiomeric purity. Purity of the enantiomers was determined via chiralHPLC, 4.6×250 mm Chiralpak AD, 10μ column, 215 nm wavelength, mobilephase: ethanol, isocratic elution at 1 mL/min at ambient temperature.

TABLE 1 Stationary Phase ChiralPak AD, 20μ Column Dimension/Temp 5 × 10cm/30° C. Mobile Phase 100% ethanol Feed Concentration   75 g/L inmobile phase Feed Rate  4.0 mL/min Eluant Rate 90.5 mL/min RaffinateRate 35.6 mL/min Extract Rate 58.9 mL/min Recycling Rate  262 mL/minPeriod Time  1.0 min

Enantiomer 1 was determined to be Ethyl(2R)-4-bromo-2-methyl-2-(methylsulfonyl)butanoate.

Preparation 1B Benzyl (+/−)-4-bromo-2-methyl-2-(methylsulfonyl)butanoateand Individual Enantiomers (R) and (S) Step A) Benzyl 2-chloropropanoate

Benzyl alcohol (242 mL, 253 g, 2.34 mol) and pyridine (204 mL, 204 g,2.57 mol) were dissolved in methylene chloride (2.5 L) and cooled to 0°C. 2-Chloropropanoyl chloride (250 mL, 327 g, 2.57 mol) was addeddropwise keeping the temperature between 0° C. and 5° C. After additionthe mixture was allowed to warm to RT overnight. The mixture was washedwith 20% aqueous citric acid (2.5 L), saturated aqueous NaHCO₃ (2.5 L),brine (2.5 L), dried (MgSO₄), filtered and concentrated in vacuo. Theresulting brown liquid (450 g) was dissolved in a small amount ofmethylene chloride and filtered through a short path of silica gel.After concentration, the crude was purified via bulb-to-bulbdistillation (2*10−2 mbar, 90-95° C.) affording the title compound as apale yellow liquid (420 g, 90%). ¹H-NMR: (CDCl₃, 300 MHz): δ ppm 1.75(d, 3H, CH₃), 4.45 (q, 1H, CHCl), 5.25 (s, 2H, CH2Ar), 7.40 (m, 5H,ArH).

Step B) Benzyl 2-(methylsulfonyl)propanoate

Benzyl 2-chloropropanoate was converted to the title compound followingthe general procedure outlined for ethyl 2-(methylsulfonyl)propanoate inPreparation 1A. The title compound was obtained as a yellow liquid (389g, 70%). ¹H-NMR: (CDCl3, 300 MHz): δ ppm 1.65 (dt, 3H, CHCH₃), 3.00 (s,3H, SO₂CH₃), 3.95 (q, 1H, CH), 5.25 (m, 2H, CO2CH2Ar), 7.40 (m, 5H,ArH).

Step C) Benzyl (+/−)-4-bromo-2-methyl-2-(methylsulfonyl)butanoate

Benzyl 2-(methylsulfonyl)propanoate was converted to the title compoundfollowing the general procedure outlined for ethyl(+/−)-4-bromo-2-methyl-2-(methylsulfonyl)butanoate in Preparation 1A.The title compound was obtained as a pale yellow liquid (300 g, 58%).¹H-NMR: (CDCl3, 300 MHz): δ ppm 1.70 (s, 3H, CH₃), 2.60 (m, 1H,CH₂CH₂Br), 2.80 (m, 1H, CH₂CH₂Br), 3.00 (s, 3H, SO₂CH₃), 3.35 (m, 1H,CH₂CH₂Br), 3.50 (m, 1H, CH₂CH₂Br), 5.30 (m, 2H, CO₂CH₂Ar), 7.40 (m, 5H,ArH)

Step D) Chiral Separation of Benzyl(+/−)-4-bromo-2-methyl-2-(methylsulfonyl)butanoate

Benzyl (+/−)-4-bromo-2-methyl-2-(methylsulfonyl)butanoate (275g) wasdissolved in isopropanol/acetonitrile (900 mL) and resolved using anAnalytical SFC-4 instrument, AS-H column (30×250), a CO₂/Propanol(90/10) mobile phase, with a flow rate of 120g/min to afford enantiomer1 (98 g, rt=3.09 min, [α]₅₈₉ ²⁰=−13.9°) at 99.94% enantiomeric purityand enantiomer 2 (101.5 g, rt=4.18 min, [α]₅₈₉ ²⁰=+11.61°) at 97.77%enantiomeric purity.

(S)-benzyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate

¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.65 (s, 3 H) 2.48-2.60 (m, 1 H)2.74-2.86 (m, 1 H) 2.95 (s, 3 H) 3.25-3.37 (m, 1 H) 3.40-3.52 (m, 1 H)5.16-5.31 (m, 2 H) 7.31-7.40 (m, 5 H)

[α]₅₈₉ ²⁰=−13.9°

(R)-benzyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate

¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.67 (s, 3 H) 2.51-2.61 (m, 1 H)2.75-2.87 (m, 1 H) 2.97 (s, 3 H) 3.28-3.37 (m, 1 H) 3.40-3.60 (m, 1 H)5.15-5.36 (m, 2 H) 7.30-7.48 (m, 5 H)

[α]₅₈₉ ²⁰=+11.61°

Preparation 2

Scheme 2 below illustrates the preparation of4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideand its corresponding R-enantiomer. The reaction sequence in Preparation2B, is the same with the exception that benzyl(2R)-4-bromo-2-methyl-2-(methylsulfonyl)butanoate is used as a startingmaterial in order to arrive at the desired enantiomer.

Preparation 2A Synthesis of Compound VI (T3):4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideas a Mixture of Diastereoisomers

Step A) 4-iodopyridin-2(1H)-one (Compound III)

2-fluoro-4-iodopyridine (2.21 kg, 9.91 mol) was suspended in a mixtureof acetic acid (7 L) and H₂O (3.5 L) with mechanical stirring. Themixture was heated at reflux overnight. After cooling to roomtemperature the solid was filtered off and concentrated in vacuo. Theresidue was stirred in Et₂O (3 L), the title compound (1.72 kg, 7.78mol) was collected by filtration as a pale yellow solid. ¹H-NMR:(DMSO-d₆, 300 MHz): δ 6.50 (d, 1H), 6.85 (s, 1H), 7.15 (d, 1H), 11.80(s, 1H)

Step B) Compound IV(T1): ethyl4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate(A=Et)

To a mixture of 4-iodopyridin-2(1H)-one (3.9 g, 18 mmol), which may beproduced in Step A above, and cesium carbonate (11.9 g, 35.3 mmol) intetrahydrofuran (176 mL) at ambient temperature was added ethyl4-bromo-2-methyl-2-(methylsulfonyl)butanoate (6.08 g, 21.2mmol)(Compound II). The mixture was heated to 50° C. and stirredovernight. The mixture was allowed to cool to ambient temperature andfiltered through a celite pad. The pad was washed with methylenechloride and the filtrate was concentrated in vacuo. The crude oil waspurified via silica gel chromatography, eluting with heptanes/ethylacetate. The desired fractions were isolated, the solvent removed viarotary evaporation ethyl4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate asa solid. 4.73 g. LCMS: (M+1) 428.2

Step C) Compound (V)T2:4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid

To a solution of ethyl4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate(3.26 g, 7.63 mmol), which may be produced as in Step B above, intetrahydrofuran/methanol (4:1, 60 mL) at ambient temperature was added asolution of lithium hydroxide monohydrate (0.9 M in water, 15.3 mmol).The resulting mixture was stirred at ambient temperature for 3 hours.The mixture was acidified with aqueous hydrochloric acid (1 N, 16 mL)and extracted three times with methylene chloride. The combined organicextracts were dried over magnesium sulfate, filtered and concentrated invacuo to afford4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid as a solid. 3.05 g.

LCMS: (M+1) 400.1

Step D) Compound (VI) T3:4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

To a solution of4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid (3.01 g, 7.54 mmol), which may be produced as in Step C above, inmethylene chloride (75 mL) at ambient temperature was added1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.02 g,10.6 mmol), 1-hydroxy benzotriazole monohydrate (2.08 g, 13.6 mmol),triethyl amine (1.89 mL, 13.6 mmol) andO-tetrahydro-2H-pyran-2-yl-hydroxylamine (1.33 g, 11.3 mmol). Theresulting mixture was stirred at ambient temperature overnight. Themixture was diluted with methylene chloride and water. The phases wereseparated and the aqueous extracted with methylene chloride two times.The organic extracts were combined and dried over magnesium sulfate,filtered and concentrated in vacuo to a crude residue. The crude residuewas purified via silica gel chromatography eluting with methylenechloride and methanol. The fractions containing desired product werecombined and concentrated to afford4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideas a solid. 3.62 g LCMS: (M−1) 497

Preparation 2B Synthesis of T6:(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Step A) T4: Benzyl(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

To a mixture of 4-iodopyridin-2(1H)-one which may be produced as in StepA of Preparation 2A (32.9 g, 149 mmol) and cesium carbonate (102 g, 312mmol) in tetrahydrofuran (400 mL) at ambient temperature was addedbenzyl (2R)-4-bromo-2-methyl-2-(methylsulfonyl)butanoate (62.3 g, 178.4mmol). The mixture was heated to 60° C. and stirred overnight. Themixture was allowed to cool to ambient temperature and filtered througha celite pad. The pad was washed with ethyl acetate (500 mL), thefiltrates combined and concentrated in vacuo to afford an orange oil.The crude oil was purified via filtration through a silica gel pad,eluting with heptanes/ethyl acetate. The desired fractions were isolatedand the solvent was removed via rotary evaporation affording benzyl(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoateas a white solid. 44.91 g.

¹NMR (CDCl₃): 7.39-7.36 (5H, m), 7.03 (1H, d, J=1.76 Hz), 6.77 (1H, d,J=7.03 Hz), 6.41 (1H, dd, J=1.76 Hz, J=7.03 Hz), 5.21 (2H, d, J=1.56Hz), 4.19-4.12 (1H, m), 3.82-3.75 (1H, m), 2.97 (3H, s), 2.47-2.42 (2H,m), 1.73 (3H, s) ppm.

Step B) T5:(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid

To a solution of benzyl(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate(44.91 g, 91.7 mmol), which may be produced as in Step A above, intetrahydrofuran (300 mL) and methanol (300 mL) at ambient temperaturewas added potassium hydroxide (3.76 M in water, 564 mmol). The resultingmixture was stirred at ambient temperature for 16 hours. The solvent wasremoved via rotary evaporation and the residue was dissolved in water.The aqueous layer was washed with diethyl ether and then acidified withconcentrated hydrochloric acid (˜pH 2) which afforded a whiteprecipitate. The precipitate was collected via filtration, washed withwater and dried in vacuo to a constant weight affording(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid as a white solid. 33.2 g. LCMS: (M+1) 400.4 ¹NMR (CD₃OD): 7.34 (1H,d, J=7.23), 7.03 (1H, d, J=1.76), 6.69 (1H, dd, J=1.95, J=7.23),4.24-4.16 (1H, m), 4.05-3.98 (1H, m), 3.14 (3H, s), 2.57-2.50 (1H, m),2.35-2.28 (1H, m), 1.68 (3H, s) ppm.

Step C) T6:(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

To a solution of(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid, which may be produced as in Step B above, (33.18 g, 83.12 mmol) inmethylene chloride (400 mL) at ambient temperature was added1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (22.3 g, 116mmol), 1-hydroxy benzotriazole monohydrate (22.9 g, 150 mmol), triethylamine (20.9 mL, 150 mmol) and O-tetrahydro-2H-pyran-2-yl-hydroxylamine(14.6 g, 125 mmol). The resulting mixture was stirred at ambienttemperature overnight. The mixture was diluted with methylene chlorideand water. The phases separated and the aqueous extracted with methylenechloride two times. The organic extracts were combined and dried overmagnesium sulfate, filtered and concentrated to a crude residue. Thecrude residue was dissolved in methylene chloride (˜150 mL) with minimalmethanol. To this solution was added heptanes (450 mL) and the mixturewas concentrated in vacuo to 150 mL and filtered. The solid was washedwith heptanes and dried in vacuo to give(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide.26.1 g LCMS: (M−1) 497.6

Preparation 3 Synthesis of T8:(2R)-4-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Step A) T7:(R)-4-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid

Neopentyl diboron (9.4 g, 28 mmol), KOAc (7.1 g, 69 mmol, 3 eq.) andPd(dppf)Cl₂ (532 mg, 0.69 mmol, 0.03 eq.) was added into a 200 mL roundbottom flask equipped with a magnetic stirrer and a 120 mL additionfunnel. The product of Step B of Preparation 2B,(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid T5 (9.2 g, 23 mmol, 1.0 equiv.) was added into the addition funnel.The system was purged with nitrogen/vacuum and kept under nitrogen.Degassed DMSO (45 mL) was added into the addition funnel. The system wasagain purged with N₂ for 5 mins. The T5 solution was added to thereaction mixture over 2 mins at room temperature then heated to 80° C.and maintained at that temperature for a further hour. The reactionmixture was cooled to RT and poured into 100 mL water. Mixture wasadjusted to pH 3 with 6 N HCl and refrigerated for 30 min. A dark solidformed and was collected via filtration and dried under high vacuum overP₂O₅for 3 days to yield 13 g of solid product. The solid was suspendedin 100 mL MeOH, 16 g silica gel was added and mixture was concentratedin vacuo. The preabsorbed material was packed into a cartridge, loadedonto an 80 g silica gel column and purified using 0 to 20% MeOH in DCM(product eluted out at ˜8% MeOH) in 45 min at 60 mL/min flow rate. Thedesired fractions were concentrated to furnish 6.3 g off white solid(71%). LCMS m/z 318.0 (M−neopentyl+H), 396.1 (M−neopentyl +DMSO+H); ¹HNMR (400 MHz, DMSO-d₆) δ ppm 0.93 (s, 6 H) 1.54 (s, 3 H) 2.14 (ddd,J=13.04, 10.69, 4.79 Hz, 1 H) 2.38 (ddd, J=13.18, 10.45, 5.86 Hz, 1 H)3.16 (s, 3 H) 3.73 (s, 4 H) 3.77-3.92 (m, 1 H) 4.05 (ddd, J=12.40,10.74, 4.98 Hz, 1 H) 6.33 (dd, J=6.74, 1.27 Hz, 1 H) 6.62 (s, 1 H) 7.59(d, J=6.84 Hz, 1 H) 13.87 (br. s., 1 H).

Step B) T8:(2R)-4-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

To a suspension of the product of Step A above, T 7, (5.0 g, 13 mmol) in200 mL THF was added N-methyl morpholine (2.0 g, 20 mmol) and2-chloro-4,6-dimethoxy-1,3,5-triazine (2.6 g, 14 mmol). The reactionmixture was stirred at room temperature for 2 h.O-tetrahydro-2H-pyran-2-yl-hydroxylamine was added to the resultingmixture and was stirred at RT for 3 hrs. The solids were filtered andthe filtrate was concentrated in vacuo to low volume ˜20 mL, 20 mL EtOAcwas added to the liquid and the resulting mixture was kept inrefrigerator for 20 h. The resulting white solid was collected viafiltration and dried to furnish 2.82 g of the title compound. LCMS m/z341.71 (M−neopentyl+H).

Preparation 44-(4-bromo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(Mixture of Diastereoisomers)

T9:4-(4-bromo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

The title compound was made via a method analogous to the preparation ofT3 in Preparation 2A, Step D, except that 4-bromopyridin-2(1H)-one wasused instead of 4-iodopyridin-2(1H)-one with comparable yields.

m/z+ was 367

Example 1(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1H-pyrazol-1-yl)phenyl]pyridin-1(2H)-yl}butanamide

Step A)1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1H-pyrazole

1-(4-bromophenyl)-1H-pyrazole (0.34 g, 1.5 mmol),bis(pinacolato)diborane (0.53 g, 2.1 mmol) and potassium acetate (446mg, 4.5 mmol) were combined in a 4 dram vial in 10 mL dioxane. Thereaction mixture was bubbled with nitrogen for 10 minutes thenPd(dppf)Cl₂ (110 mg, 0.15 mmol) was added. The reaction was heated at100° C. overnight. The reaction was diluted with 20 mL of EtOAc and 20mL of 1:1 saturated sodium bicarbonate/water. The organic layer wasisolated and the aqueous layer was back-extracted once with 10 mL ofEtOAc. The organic layers were combined, dried over solid magnesiumsulfate, filtered and concentrated. The crude material was purified byeluting the material through a short pad of silica gel with EtOAc toprovide a dark solid (0.42 g, 100%). MS (LCMS) m/z 271.4 (M+1). ¹H NMR(400 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 6.46 (dd, J=2.54, 1.76 Hz,1 H) 7.68-7.72 (m, 2 H) 7.72 (d, J=1.76 Hz, 1 H) 7.85-7.90 (m, 2 H) 7.96(d, J=1.76 Hz, 1 H).

Step B)(2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1H-pyrazol-1-yl)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Trisdibenzylidine dipalladium (29 mg, 0.049 mmol) was added to a mixtureof potassium carbonate (343 mg, 2.46 mmol),1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1H-pyrazole(133 mg, 0.49 mmol) and(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(245 mg, 0.49 mmol), which may be synthesized as described inPreparation 2B in 1,2-dimethoxyethane-methanol (5.0 mL, 1:1). Thereaction was heated to 80° C. and allowed to stir overnight. Thereaction was diluted with ethyl acetate (10 mL), filtered through a padof Celite, and concentrated under reduced pressure. The crude materialwas purified by flash chromatography (1:0-9:1 ethyl acetate/methanol) toprovide a colorless residue (58 mg, 23%). MS (LCMS) m/z 513.7 (M−1).

Step C)(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1H-pyrazol-1-yl)phenyl]pyridin-1(2H)-yl}butanamide

A solution of hydrochloric acid (3.0 mL, 4.0 M in 1,4-dioxane) was addeddropwise to a solution of(2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1H-pyrazol-1-yl)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(58 mg, 0.11 mmol) in dichloromethane (3.0 mL) and methanol (0.6 mL) at0° C. After 2 h, the reaction was concentrated under reduced pressure.The resulting residue was triturated with diethyl ether, filtered,washed with heptane, and dried under reduced pressure to provide a lightyellow solid (47 mg, 98%). MS (APCI) m/z 431.3 (M+1). ¹H NMR (400 MHz,CD₃OD) δ ppm 1.71 (s, 3H), 2.36-2.43 (m, 1H), 2.59-2.68 (m, 1H), 3.09(s, 3H), 3.96-4.05 (m 1H), 4.30-4.40 (m, 1H), 6.56 (dd, J=1.8, 2.3 Hz,1H), 6.93-6.95 (m, 2H), 7.76 (d, J=1.8 Hz, 1H), 7.82-7.92 (m, 5H), 8.31(d, J=2.3, 1H).

Example 2(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[(E)-2-phenylvinyl]pyridin-1(2H)-yl}butanamide

Step A)(2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[(E)-2-phenylvinyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Pd EnCat™ (133 mg, 0.04 mmol, 0.1 equiv), was added to a mixture ofpotassium carbonate (166 mg, 1.2 mmol, 3.0 equiv),[(E)-2-phenylvinyl]boronic acid (65 mg, 0.44 mmol, 1.1 equiv), and(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(200 mg, 0.40 mmol), which may be synthesized as described Preparation2B, in 2:1 1,4-dioxane-water (3.6 mL). The reaction was heated to 80° C.and allowed to stir overnight. The reaction was diluted with ethylacetate (10 mL), filtered through a pad of Celite, and concentratedunder reduced pressure. The crude material was purified by flashchromatography ((1:1-0:1 heptane/ethyl acetate) to provide a whiteresidue (90 mg, 47%). MS (LCMS) m/z 473.7 (M−1).

Step B)(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[(E)-2-phenylvinyl]pyridin-1(2H)-yl}butanamide

A solution of hydrochloric acid (2.5 mL, 4.0 M in 1,4-dioxane) was addedto a solution of(2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[(E)-2-phenylvinyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(40 mg, 0.084 mmol) in 5:1 dichloromethane-methanol (2.5 mL) at 0° C.After 4 h, the reaction was concentrated under reduced pressure. Theresulting residue was triturated with 1:1 pentane-diethyl ether,filtered, washed with pentane and dried under reduced pressure toprovide a light yellow solid (33 mg, 76%). MS (LCMS) m/z 391.4 (M+1). ¹HNMR (400 MHz, METHANOL-d₄) δ ppm 1.69 (s, 3 H) 2.30-2.42 (m, 1 H)2.56-2.69 (m, 1 H) 3.08 (s, 3 H) 3.93-4.06 (m, 1 H) 4.32 (td, J=11.76,4.98 Hz, 1 H) 6.75 (s, 1 H) 7.00 (d, J=6.24 Hz, 1 H) 7.11 (d, J=16.39Hz, 1 H) 7.30-7.42 (m, 3 H) 7.47 (d, J=16.39 Hz, 1 H) 7.62 (d, J=7.02Hz, 2 H) 7.75 (s, 1 H)

Example 3(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2-phenylethyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Step A)(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2-phenylethyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Palladium (20 mg, 5% on activated carbon) was added to a nitrogen-purgedsolution of(2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[(E)-2-phenylvinyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(50 mg, 0.10 mmol), which may be produced as in Example 2, Step A, and1,4-cyclohexadiene (0.20 mL, 2.1 mmol, 20.0 equiv) in ethanol (2 mL) atroom temperature. The reaction was allowed to stir for 3 days. Themixture was filtered through a plug of silica, washed with ethylacetate, and the resulting filtrate was concentrated under reducedpressure. The crude material was purified by flash chromatography((1:1-0:1 heptane/ethyl acetate) to provide a colorless oil (14 mg,28%). MS (LCMS) m/z 475.7 (M−1).

Step B)(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2-phenylethyl)pyridin-1(2H)-yl]butanamide

A solution of hydrochloric acid (1.0 mL, 4.0 M in 1,4-dioxane) was addedto a solution of(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2-phenylethyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(14 mg, 0.029 mmol) in 5:1 dichloromethane-methanol (1.2 mL) at 0° C.After 2 h, the reaction was concentrated under reduced pressure. Theresulting residue was triturated with 1:1 pentane-dichloromethane,filtered, washed with pentane, and dried under reduced pressure toprovide a light pink solid (8 mg, 70%). MS (APCI) m/z 393.3 (M+1). ¹HNMR (400 MHz, DMSO-d₆) δ ppm 1.51 (s, 3 H) 2.00-2.14 (m, 1 H) 2.24-2.36(m, 1 H) 2.63-2.74 (m, 2 H) 2.78-2.88 (m, 2 H) 3.06 (s, 3 H) 3.58-3.73(m, 1 H) 3.94-4.08 (m, 1 H) 6.16-6.26 (m, 2 H) 7.11-7.32 (m, 5 H) 7.55(d, J=7.41 Hz, 1 H) 11.14 (br s, 1 H).

Example 4(+/−)-4-[4-{4-[3-(4,4-Difluoropiperidin-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamidehydrochloride

Step A) 1-bromo-4-(3-bromopropoxy)benzene

A suspension of 4-bromophenol (10.0 g, 58 mmol), 1,3-dibromopropane(14.0 g, 69.4 mmol) and potassium carbonate (16.0 g, 116 mmol) inDMF/THF (1:1, 200 mL) was heated to 60° C. over night. The reaction waspoured into water and extracted with ether (2×200 mL). The organiclayers were combined and washed with water (4×200 mL) and brine (2×200mL). The organic layer was dried (Na₂SO₄), filtered and concentrated.Upon concentration a white solid precipitated, the solid was removed byfiltration. The filtrate was concentrated and purified by flash columnchromatography on an Anaolgix SF65-200g column (hexanes/ethyl acetate95:5) to afford the title compound as clear oil (6.28 g, 37%). ¹H NMR(400 MHz, CHLOROFORM-d) δ ppm 2.24-2.42 (m, 2 H) 3.50-3.64 (m, 2 H) 4.08(t, J=5.66 Hz, 2 H) 6.74-6.86 (m, 2 H) 6.75-6.84 (m, 2 H).

Step B) 1-[3-(4-bromophenoxy)propyl]-4,4-difluoropiperidine

A suspension of 1-bromo-4-(3-bromopropoxy)benzene (1.85 g, 6.29 mmol),4,4-difluoropiperidine hydrochloride (1.0 g, 6.34 mmol) and potassiumcarbonate (2.17 g, 15.7 mmol) in acetonitrile (100 mL) was heated to 60°C. overnight, then concentrated in vacuo. The residue was partitionedbetween ether and saturated aqueous sodium bicarbonate. The layers wereseparated; the organic layer was washed with saturated aqueous sodiumbicarbonate, water and brine. The organic layer was dried (Na₂SO₄),filtered and concentrated. Purification by flash column chromatographyon an analogix SF40-80g column (hexanes/ethyl acetate=7:3) afforded thetitle compound as a clear oil (1.07 g, 50%). LCMS m/z 334.3 (M+1). ¹HNMR (400 MHz, CHLOROFORM-d) δ ppm 1.90-2.08 (m, 6 H) 2.47-2.64 (m, 6 H)3.99 (t, J=6.34 Hz, 2 H) 6.75-6.81 (m, 2 H) 7.34-7.40 (m, 2 H).

Step C)4-[4-{4-[3-(4,4-difluoropiperidin-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Potassium acetate (1.26 g, 12.8 mmol) was added to a suspension of1-[3-(4-bromophenoxy)propyl]-4,4-difluoropiperidine (1.07 g, 3.20 mmol)in DMF (10 mL). After 10 minutes, bis(pinacolato)diborane (1.220 g, 4.80mmol) and dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II)(261 mg, 0.32 mmol) were added. The resulting suspension was heated to100° C. After 1 hour the reaction was concentrated and the residue wasdiluted with ethyl acetate (100 mL) and filtered through celite. Thefiltrate was washed with saturated aqueous sodium bicarbonate (2×50 mL).The organic layer was dried (Na₂SO₄), filtered and concentrated. Theresidue was dissolved in 1,4-dioxane (20 mL). Potassium carbonate (553mg, 1.00 mmol),(+/−)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2A (500 mg, 1.00 mmol) wereadded, followed by water (2.0 mL). A clear solution resulted, Pd EnCat™(513 mg, 0.20 mmol) was added and the resulting suspension was heatedovernight at 80° C. After 16 hours the reaction was diluted with ethylacetate (100 mL) and filtered through celite. The filtrate wasconcentrated the residue was triturated at room temperature for 1 hourin ethyl acetate/DCM 1:1 and filtered through celite. The filtrate wasdried (Na₂SO₄) and concentrated.

Purification by flash column chromatography on an Analogix SF40-80gcolumn (DCM/MeOH 98:2-95:5) afforded the title compound as clear oil(213 mg, 34%). LCMS m/z 627.0/542.8 (M+1)

Step D)(+/−)-4-[4-{4-[3-(4,4-difluoropiperidin-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamidehydrochloride

HCl (4.0 M in 1,4-dioxane, 1.0 mL) was added to a solution of4-[4-{4-[3-(4,4-difluoropiperidin-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(209 mg, 0.334 mmol) in 1,4-dioxane/water (1:1, 5 mL). After 10 minutesthe reaction was concentrated to give a white solid, the solid wastriturated with 2-propanol at 50° C. for 1 h. The title compound wasisolated by filtration as a white solid (146 mg, the hydrochloride salt,75%). LCMS m/z 542.8 (M+1) ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.57 (s, 3 H)2.22 (br. s., 3 H) 2.38 (br. s., 5 H) 3.11 (s, 3 H) 3.13-3.26 (m, 2 H)3.31 (br. s., 2 H) 3.74 (br. s., 3 H) 4.14 (t, J=5.76 Hz, 3 H) 6.59-6.72(m, 2 H) 7.05 (d, J=8.78 Hz, 2 H) 7.63-7.79 (m, 3 H) 11.03 (br. s., 1 H)11.18 (br. s., 1 H)

Example 5(2R)-N-hydroxy-4-{4-[4-(cis-3-hydroxcyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide

Step A)Cis-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutanol

A solution of cis-3-(4-bromophenyl)cyclobutanol (0.500 g, 2.20 mmol),bis(pinacolato)diborane (0.671 g, 2.64 mmol), potassium acetate (0.864g, 8.81 mmol) and palladium dppf (89.9 mg, 0.110 mmol) in 1,4-dioxane(20 mL) was heated to reflux. After 2 hours the reaction was cooled toroom temperature, diluted with ethyl acetate and filtered throughcelite. The filtrate was concentrated the resulting residue waspartitioned between ether and water, an emulsion was removed byfiltration. The layers were separated; the organic layer was washed withwater (2×) then brine (1×). The organic layer was dried (Na₂SO₄),filtered and concentrated. Purification by flash column chromatographyon a Biotage SNAP cartridge Kp-sil 25g column (hexanes/ethylacetate=8:2) afforded the title compound (430 mg) as a clear oilcontaminated with 10% cis-3-(4-bromophenyl)cyclobutanol.

Step B)(2R)-4-{4-[4-(cis-3-hydroxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Water (1.0 mL) was added to a suspension of potassium carbonate (388 mg,2.81 mmol),(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-[(2R)-tetrahydro-2H-pyran-2-yloxy]butanamide,which may be produced as in Preparation 2B (700 mg, 1.40 mmol), andcis-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutanol(385 mg, 1.40 mmol) in 1,4-dioxane (10 mL). A clear solution resulted.Pd EnCat™ (380 mg, 0.15 mmol) was added and the resulting suspension washeated to 100° C. After 2 hours, the reaction was cooled to roomtemperature, diluted with ethyl acetate (50 mL) and filtered throughcelite eluting with ethyl acetate (50 mL). The filtrate was concentratedand the residue was partitioned between dichloromethane and water. Thelayers were separated, and the aqueous layer was extracted withdichloromethane (3×). The organic layers were combined, dried (Na₂SO₄),filtered and concentrated. Purification by flash column chromatographyon an Analogix SF25-40 g (hexanes/ethyl acetate 1:1-05:95) afforded thetitle compound as a solid (625 mg, 86%). LCMS m/z 519.2/435.2 (M+1).

Step C)(2R)-N-hydroxy-4-{4-[4-(cis-3-hydroxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide

HCl (1.0 N in water, 3.58 mL) was added to a solution of(2R)-4-{4-[4-(cis-3-hydroxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(620 mg, 1.20 mmol) in 1,4-dioxane (10 mL). After 2 hours the reactionwas concentrated to give a brown solid. The solid was triturated withethanol at 50° C., for 30 minutes. After cooling, filtration affordedthe title compound as a white solid (384 mg, 74%). LCMS m/z 435.6 (M+1).1H NMR (400 MHz, DMSO-d₆) δ ppm 1.58 (s, 3 H) 1.83-1.98 (m, 2 H)2.11-2.24 (m, 1 H) 2.44 (d, J=17.95 Hz, 1 H) 2.54-2.69 (m, 2 H)2.83-3.00 (m, 1 H) 3.11 (s, 3 H) 3.65-3.84 (m, 1 H) 3.98-4.18 (m, 2 H)6.65 (dd, J=7.02, 2.15 Hz, 1 H) 6.69 (d, J=1.95 Hz, 1 H) 7.34 (d, J=8.20Hz, 2 H) 7.62-7.71 (m, 2 H) 7.74 (d, J=7.02 Hz, 1 H) 11.17 (br. s., 1 H)

Example 6(2R)-N-hydroxy-4-{4-[4-(trans-3-hydroxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide

Step A)Trans-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutanol

A solution of trans-3-(4-bromophenyl)cyclobutanol (0.500 g, 2.20 mmol),bis(pinacolato)diborane (0.671 g, 2.64 mmol), potassium acetate (0.864g, 8.81 mmol) and[1,1′-bis-(diphenylphosphino)ferrocene]-dichloropalladium(II) dcmcomplex (89.9 mg, 0110 mmol) in 1,4-dioxane (20 mL) was heated to refluxovernight. After 16 hours the reaction was cooled to room temperature,diluted with ethyl acetate and filtered through celite. The filtrate wasconcentrated, the resulting residue was partitioned between ether andwater, and an emulsion was removed by filtration. The layers in thefiltrate were separated; the organic layer was washed with water (2×)then brine (1×). The organic layer was dried (Na₂SO₄), filtered andconcentrated.

Purification on a Biotage SNAP cartridge Kp-sil 25g column(hexanes/ethyl acetate=8:2) afforded the title compound as a clear oil(508 mg, 84%).

¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 2.35-2.62 (m, 4 H)3.54-3.71 (m, 1 H) 4.49-4.62 (m, 1 H) 7.23-7.29 (m, 3 H) 7.74-7.80 (m, 2H).

Step B)(2R)-4-{4-[4-(trans-3-hydroxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Water (1.0) was added to a suspension of potassium carbonate (499 mg,3.61 mmol),(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-[(2R)-tetrahydro-2H-pyran-2-yloxy]butanamide,which may be produced as in Preparation 2B (900 mg, 1.81 mmol), andtrans-3-[4-(4,4,5,5-tetramethyl-11,3,2-dioxaborolan-2-yl)phenyl]cyclobutanol(495 mg, 1.81 mmol) in 1,4-dioxane (10 mL). A clear solution resulted.Pd EnCat™ (482 mg, 0.19 mmol) was added and the resulting suspension washeated to 100° C. After 2 hrs the reaction was cooled to roomtemperature, diluted with ethyl acetate (50 mL) and filtered throughcelite eluting with ethyl acetate (50 mL). The filtrate concentrated andthe residue was partitioned between dichloromethane and water. Thelayers were separated and the aqueous layer was extracted withdichloromethane (3×). The organic layers were combined, dried (Na₂SO₄),filtered and concentrated. Purification on an Analogix SF25-40 g(hexanes/ethyl acetate 1:1-05:95) afforded the title compound as a solid(383 mg, 40%). LCMS m/z 517.8 (M−1).

Step C)(2R)-N-hydroxy-4-{4-[4-(trans-3-hydroxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide

HCl (1.0 N in water, 2.17 mL) was added to a solution of(2R)-4-{4-[4-(trans-3-hydroxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(375 mg, 0.723 mmol) in 1,4-dioxane (5 mL). After 1 hour, the reactionwas concentrated to give a brown solid. The solid was triturated with2-propanol at 50° C., for 30 minutes. After cooling, filtration affordedthe title compound as a white solid (187 mg, 60%).LCMS m/z 435.6 (M+1).¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.57 (s, 3 H) 2.11-2.23 (m, 1 H)2.26-2.38 (m, 4 H) 2.38-2.48 (m, 1 H) 3.11 (s, 3 H) 3.42-3.60 (m, 1 H)3.74 (td, J=12.00, 4.68 Hz, 1 H) 4.00-4.21 (m, 1 H) 4.25-4.42 (m, 1 H)6.58-6.72 (m, 2 H) 7.36 (d, J=8.20 Hz, 2 H) 7.61-7.71 (m, 2 H) 7.74 (d,J=7.22 Hz, 1 H) 11.17 (br. s., 1 H)

Example 7(2R)-N-hydroxy-4-[4-{4-[(4-hydroxycyclohexyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamideStep A) 8-(4-bromophenoxy)-1,4-dioxaspiro[4.5]decane

1,4-dioxaspiro[4.5]decan-8-ol^(ref 1) (3.6 g, 20.8 mmol) was added to asolution of 4-bromophenol (3.00 g, 18.96 mmol) in THF (20 mL).Triphenylphosphine (4.96 g, 18.9 mmol) and triethylamine (1.92 g, 18.9mmol) were added. The resulting solution was cooled to 0° C. and DIAD(3.83 g, 18.9 mmol) was added by dropwise addition. The reaction wasmaintained at 0° C. for 30 minutes then warmed to room temperature andstirred over night. The reaction was quenched by addition of water andextracted with ether (2×100 mL). The organic layers were combined andwashed with 1N NaOH (2×100 mL), then water (2×100 mL). The organic layerwas dried (Na₂SO₄), filtered and concentrated. Purification by flashcolumn chromatography on an Analogix SF40-150 g column (hexanes/ethylacetate 8:2) afforded the title compound as a white waxy solid (2.83 g,47%). ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.58-1.69 (m, 2 H) 1.85-1.98(m, 6 H) 3.92-4.02 (m, 4 H) 4.33-4.41 (m, 1 H) 6.76-6.84 (m, 2 H)7.33-7.40 (m, 2 H)

Ref 1: Journal of Organic Chemistry, 71(22), 8424-8430; 2006

Step B) 4-(4-bromophenoxy)cyclohexanone

1 N HCl_((aq)) (45 mL) was added to a solution of8-(4-bromophenoxy)-1,4-dioxaspiro[4.5]decane (2.8 g, 8.94 mmol) in THF(100 mL). The reaction was heated to 50° C. After 1 hour the reactionwas cooled to room temperature and neutralized by addition of solidsodium bicarbonate. The reaction was extracted with ether (1×), theresulting organic layer was washed with water, dried (Na₂SO₄), filteredand concentrated. Purification on a Biotage SNAP cartridge KP Sil 100g(hexanes/ethyl acetate=9:1) afforded the title compound as a white solid(2.09 g, 87%). ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.02-2.13 (m, 2 H)2.21-2.41 (m, 4 H) 2.61-2.74 (m, 2 H) 4.62-4.71 (m, 1 H) 6.81-6.89 (m, 2H) 7.37-7.44 (m, 2 H)

Step C) 4-(4-bromophenoxy)cyclohexanol

Sodium borohydride (77.3 mg, 2.04 mmol) was added to a solution of4-(4-bromophenoxy)cyclohexanone (500 mg, 1.86 mmol) in ethanol (10 mL)at room temperature. After 20 minutes the reaction was cooled to 0° C.and quenched by the addition of 1 N HCl (aq). The reaction wasconcentrated and the resulting residue was partitioned between ether and1 N HCl (aq). The layers were separated, the organic layer was washedwith water then dried (Na₂SO₄), filtered and concentrated.

Purification on an Analogix SF15-12g column (hexanes/ethyl acetate=8:2)afforded the title compound as a white solid (360 mg, 72%).

Step D)4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]cyclohexanol

A solution of 4-(4-bromophenoxy)cyclohexanol (345 mg, 1.27 mmol),bis(pinacolato)diborane (0.388 g, 1.53 mmol), potassium acetate (0.499g, 5.09 mmol) and palladium dppf (52.3 mg, 0.064 mmol) in 1,4-dioxane(10 mL) was heated to reflux. After 2 hours the reaction was cooled toroom temperature, diluted with ethyl acetate and filtered throughcelite. The filtrate was concentrated, the resulting residue waspartitioned between ether and water, and an emulsion was removed byfiltration. The layers in the filtrate were separated and the organiclayer was washed with water (2×) then brine (1×). The organic layer wasdried (Na₂SO₄), filtered and concentrated.

Purification on an Analogix SF15-12g column (hexanes/ethyl acetate=8:2)afforded the title compound as a white solid (400 mg, 99%). LCMS m/z319.6/301.6 (M+1).

Step E)(2R)-4-[4-{4-[(4-hydroxycyclohexyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Water (1.0) was added to a suspension of potassium carbonate (352 mg,2.55 mmol),(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-[(2R)-tetrahydro-2H-pyran-2-yloxy]butanamide,which may be produced as in preparation 2B (634 mg, 1.27 mmol), and4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]cyclohexanol(405 mg, 1.27 mmol) in 1,4-dioxane (10 mL). A clear solution resulted.Pd EnCat™ (344 mg, 0.13 mmol) was added and the resulting suspension washeated to 80° C. After 2 hours the reaction was cooled to roomtemperature, diluted with ethyl acetate (50 mL) and filtered throughcelite eluting with ethyl acetate (50 mL). The filtrate was concentratedand the residue was partitioned between dichloromethane and water. Thelayers were separated and the aqueous layer was extracted withdichloromethane (3×). The organic layers were combined, dried (Na₂SO₄),filtered and concentrated. Purification by flash column chromatographyon an Analogix SF25-40 g (hexanes/ethyl acetate 1:1-05:95) afforded thetitle compound as solid (444 mg, 62%). LCMS m/z 563.8/479.7 (M+1)

Step F)(2R)-N-hydroxy-4-[4-{4-[(4-hydroxycyclohexyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

HCl (1.0 N in water, 2.37 mL) was added to a solution of the(2R)-4-[4-{4-[(4-hydroxycyclohexyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(444 mg, 0.789 mmol) in 1,4-dioxane (5 mL). After 1 hour the reactionwas concentrated to give a brown solid. The solid was triturated withethanol at 50° C., for 30 minutes. After cooling, filtration affordedthe title compound as a white solid (203 mg, 54%).LCMS m/z 479.7 (M+1)

Example 8(2R)-N-hydroxy-4-[4-{4-[(cis-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamideStep A) Ethyl 4-(tetrahydro-2H-pyran-2-yloxy)cyclohexanecarboxylate

Pyridinium-4-toluenesulfonate (2.57 g, 10.2 mmol) was added to asolution of ethyl 4-hydroxycyclohexanecarboxylate (8.8 g, 51.10 mmol)and 3,4-dihydro-2H-pyran (8.60 g, 102 mmol) in DCM (200 mL). After 16hours the reaction was quenched with saturated aqueous sodiumbicarbonate. The layers were separated and the organic layer was washedwith water. The organic layer was dried (Na₂SO₄), filtered andconcentrated. Purification by flash column chromatography on an AnalogixSF65-200g column (hexanes/ethyl acetate 95:05-9:1) afforded the titlecompound (clear oil) as a mixture of isomers (11.1 g, 85%).

Step B) (+/−)-[cis-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methanoland (+/−)-[trans-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methanol

Sodium borohydride (3.69 g, 97.5 mmol) was added to a solution of ethyl4-(tetrahydro-2H-pyran-2-yloxy)cyclohexanecarboxylate (2.50 g, 9.75mmol) in ethanol (100 mL) at 0° C. The reaction was allowed to warm toroom temperature as the ice bath expired. After 2 days the reaction wascooled to 0° C. and quenched by addition of 1 N HCl until theeffervescence ceased(pH 5-6). The reaction was concentrated and theresulting residue was partitioned between ethyl acetate and water. Thelayers were separated and the aqueous layer was extracted with ethylacetate (1×). The organic layers were combined, dried (MgSO₄), filteredand concentrated. Purification on a Biotage SNAP cartridge Kp-sil 100gcolumn (hexanes/ethyl acetate=9:1-6:4) afforded the cis and transcyclohexylmethanols as clear oils.

(+/−)-[cis-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methanol (387 mg,18%)

¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.30-1.65 (m, 12 H) 1.64-1.76 (m, 1H) 1.76-1.94 (m, 3 H) 3.33-3.64 (m, 3 H) 3.80-4.01 (m, 2 H) 4.59-4.75(m, 1 H).

(+/−)-[trans-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methanol

¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.86-1.11 (m, 2 H) 1.16-1.31 (m, 1H) 1.31-1.64 (m, 7 H) 1.64-1.77 (m, 1 H) 1.78-1.93 (m, 3 H) 1.99-2.14(m, 2 H) 3.35-3.67 (m, 4 H) 3.80-4.04 (m, 1 H) 4.63-4.79 (m, 1 H).

Step C)(+/−)-2-({cis-4-[(4-bromophenoxy)methyl]cyclohexyl}oxy)tetrahydro-2H-pyran

4-Bromophenol (0.344 g, 2.0 mmol) was added to a solution of(+/−)-[cis-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methanol (0.387 g,1.81 mmol) in THF (10 mL). Triphenylphosphine (0.474 g, 1.81 mmol) andtriethylamine (0.183 g, 1.81 mmol) were added. The resulting solutionwas cooled to 0° C. and DIAD (0.365 g, 1.81 mmol) was added by dropwiseaddition. After 18 hours the reaction was quenched by addition of waterand extracted with ether (2×100 mL). The organic layers were combinedand washed with 1N NaOH (2×100 mL) then water (2×100 mL). The organiclayer was dried (MgSO₄), filtered and concentrated to give a clear oil.Purification by flash column chromatography on a Biotage SNAP cartridgeKp-sil 100g column (hexanes/ethyl acetate 9:1) afforded the titlecompound as a white solid (324 mg, 48%). ¹H NMR (400 MHz, CHLOROFORM-d)δ ppm 1.41-1.75 (m, 11 H) 1.75-1.98 (m, 4 H) 3.39-3.54 (m, 1 H)3.70-3.80 (m, 2 H) 3.83-3.97 (m, 2 H) 4.55-4.69 (m, 1 H) 6.66-6.82 (m,2H) 7.29-7.42 (m, 2 H).

Step D)(+/−)-2-[(cis-4-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}cyclohexyl)oxy]tetrahydro-2H-pyran

A solution of(+/−)-2-({cis-4-[(4-bromophenoxy)methyl]cyclohexyl}oxy)tetrahydro-2H-pyran(0.3 g, 0.812 mmol), bis(pinacolato)diborane (0.247 g, 0.974 mmol),potassium acetate (0.319 g, 3.25 mmol) and[1,1′-bis-(diphenylphosphino)ferrocene]-dichloropalladium(II) dcmcomplex (33.5 mg, 0.041 mmol) in 1,4-dioxane (10 mL) was heated toreflux. After 28 hours the reaction was concentrated. The residue waspartitioned between ether and water, an emulsion was removed byfiltration. The layers in the filtrate were separated. The organic layerwas washed with water (2×) then brine (1×). The organic layer was dried(Na₂SO₄), filtered and concentrated. Purification on a Biotage SNAPcartridge Kp-sil 10 g column (hexanes/ethyl acetate 95:5) afforded thetitle compound as a white solid (190 mg, 56%). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.30-1.38 (m, 12 H) 1.39-1.78 (m, 11 H) 1.78-1.97(m, 4 H) 3.44-3.56 (m, 1 H) 3.84 (dd, J=6.74, 1.66 Hz, 2 H) 3.88-4.00(m, 2 H) 4.61-4.75 (m, 1 H) 6.85-6.94 (m, 2 H) 7.67-7.80 (m, 2 H)

Step E)(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-{[cis-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methoxy}phenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Water (1.0) was added to a suspension of potassium carbonate (116 mg,0.842 mmol),(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-[(2R)-tetrahydro-2H-pyran-2-yloxy]butanamide,which may be produced as in Preparation 2B (210.0 mg, 4.21 mmol), and(+/−)-2-[(cis-4-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}cyclohexyl)oxy]tetrahydro-2H-pyran(175 mg, 4.21 mmol) in 1,4-dioxane (10 mL). A clear solution resulted.Pd EnCat™ (113 mg, 0.044 mmol) was added and the resulting suspensionwas heated to 100° C. After 1 hour the reaction was cooled to roomtemperature, diluted with ethyl acetate (50 mL) and filtered throughcelite eluting with ethyl acetate (50 mL). The filtrate was concentratedand the residue was partitioned between ethyl acetate and brine. Thelayers were separated and the aqueous layer was extracted with ethylacetate (3×). The organic layers were combined, dried (Na₂SO₄), filteredand concentrated. Purification on an Analogix SF15-12 g column(hexanes/ethyl acetate=1:9) afforded the title compound as solid (140mg, 50%). LCMS m/z 659.8 (M−1).

Step F)(2R)-N-hydroxy-4-[4-{4-[(cis-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

HCl (1.0 N in water, 1.02 mL) was added to a solution of(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-{[cis-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methoxy}phenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(135 mg, 0.204 mmol) in 1,4-dioxane (5.0 mL). After 1 hour the reactionwas concentrated to give a white solid. The solid was triturated withethanol at 50° C., for 30 minutes. After cooling, filtration affordedthe title compound as a white solid (90 mg, 90%). LCMS m/z 493.7 (M+1).¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.38-1.70 (m, 12 H) 1.79 (br. s., 1 H)2.09-2.24 (m, 1 H) 2.42 (ddd, J=13.07, 11.12, 4.68 Hz, 1 H) 3.12 (s, 3H) 3.68-3.83 (m, 2 H) 3.87 (d, J=6.63 Hz, 2 H) 4.10 (d, J=6.44 Hz, 1 H)6.55-6.75 (m, 2 H) 6.94-7.10 (m, 2 H) 7.61-7.80 (m, 3 H) 11.15 (br. s.,1 H)

Example 9(2R)-N-hydroxy-4-[4-{4-[(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

Step A)(+/−)-2-({trans-4-[(4-bromophenoxy)methyl]cyclohexyl}oxy)tetrahydro-2H-pyran

The title compound (987 mg, 70.3%) was prepared from(+/−)-[trans-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methanol (815 mg,3.80 mmol) and 4-bromophenol (0.724 g, 4.18 mmol) by a procedureanalogous to that described for(+/−)-2-({cis-4-[(4-bromophenoxy)methyl]cyclohexyl}oxy)tetrahydro-2H-pyran,Example 8, Step C. ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.02-1.35 (m, 3H) 1.36-1.64 (m, 5 H) 1.66-1.90 (m, 3 H) 1.90-2.01 (m, 2 H) 2.02-2.18(m, 2 H) 3.51 (dt, J=11.02, 5.22 Hz, 1 H) 3.61 (tt, J=10.98, 4.24 Hz, 1H) 3.68-3.78 (m, 2 H) 3.88-4.00 (m, 1 H) 4.68-4.79 (m, 1 H) 6.71-6.82(m, 2 H) 7.31-7.42 (m, 2 H)

Step B)(+/−)₂-[(trans-4-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}cyclohexyl)oxy]tetrahydro-2H-pyran

The title compound (624 mg, 61.5 mmol) was prepared from(+/−)-2-({trans-4-[(4-bromophenoxy)methyl]cyclohexyl}oxy)tetrahydro-2H-pyran(900 mg, 2.44 mmol) and bis(pinacolato)diborane (742 mg, 2.92 mmol) by aprocedure analogous to that described for(+/−)-2-[(cis-4-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}cyclohexyl)oxy]tetrahydro-2H-pyran,Example 8, Step D. ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.03-1.63 (m, 20H) 1.65-1.90 (m, 3 H) 1.90-2.01 (m, 2 H) 2.03-2.15 (m, 2 H) 3.45-3.55(m, 1 H) 3.55-3.67 (m, 1 H) 3.72-3.85 (m, 2 H) 3.89-3.97 (m, 1 H)4.70-4.79 (m, 1 H) 6.88 (d, J=8.78 Hz, 2 H) 7.74 (d, J=8.78 Hz, 2 H)

Step C)(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-{[trans-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methoxy}phenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

The title compound (489 mg, 49.7%) was prepared from(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-[(2R)-tetrahydro-2H-pyran-2-yloxy]butanamide(742 mg, 1.49 mmol) and2-[(trans-4-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}cyclohexyl)oxy]tetrahydro-2H-pyran(620 mg, 1.49 mmol) by a procedure analogous to that described for(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-{[cis-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methoxy}phenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,Example 8, Step E. LCMS m/z 659.8 (M−1).

Step D)(2R)-N-hydroxy-4-[4-{4-[(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

The title compound (300 mg, 83%) was prepared from(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-{[trans-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methoxy}phenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(480 mg, 0.726 mmol) by a procedure analogous to that described for(2R)-N-hydroxy-4-[4-{4-[(cis-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamideExample 8, Step F. LCMS m/z 493.7 (M+1)H NMR (400 MHz, DMSO-d₆) δ ppm0.92-1.23 (m, 4 H) 1.54 (s, 3 H) 1.58-1.72 (m, 1 H) 1.81 (br. s., 4 H)2.06-2.21 (m, 1 H) 2.41 (s, 1 H) 3.08 (s, 3 H) 3.25-3.41 (m, 1 H) 3.74(br. s., 1 H) 3.80 (d, J=6.44 Hz, 2 H) 3.98-4.17 (m, 1 H) 6.48-6.71 (m,2 H) 6.85-7.06 (m, 2 H) 7.52-7.78 (m, 3 H) 11.15 (s, 1 H)

Example 10(2R)-4-[4-{2-Fluoro-4-[(trans-4-hydroxcyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A)(+/−)-2-({trans-4-[(4-bromo-3-fluorophenoxy)methyl]cyclohexyl}oxy)tetrahydro-2H-pyran

The title compound (885 mg, 81.6%) was prepared from(+/−)-[trans-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methanol (600 mg,2.80 mmol) and 4-bromo-3-fluorophenol (588 mg, 3.08 mmol) by a procedureanalogous to that described for(+/−)-2-({cis-4-[(4-bromophenoxy)methyl]cyclohexyl}oxy)tetrahydro-2H-pyranin Example 8, Step C. ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.03-1.21 (m,2 H) 1.21-1.36 (m, 1 H) 1.35-1.50 (m, 1 H) 1.49-1.66 (m, 4 H) 1.65-1.99(m, 5 H) 2.03-2.17 (m, 2 H) 3.44-3.55 (m, 1 H) 3.60 (tt, J=10.98, 4.24Hz, 1 H) 3.72 (d, J=6.24 Hz, 2 H) 3.86-4.00 (m, 1 H) 4.70-4.80 (m, 1 H)6.59 (ddd, J=8.88, 2.83, 0.98 Hz, 1 H) 6.68 (dd, J=10.54, 2.73 Hz, 1 H)7.35-7.44 (m, 1 H)

Step B)(+/−)-2-[(trans-4-{[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}cyclohexl)oxy]tetrahydro-2H-pyran

The title compound (366 mg, 37.1%) was prepared from(+/−)-2-({trans-4-[(4-bromo-3-fluorophenoxy)methyl]cyclohexyl}oxy)tetrahydro-2H-pyran(0.88 g, 2.27 mmol) and bis(pinacolato)diborane (0.692 g, 2.73 mmol) bya procedure analogous to that described for(+/−)-2-[(cis-4-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}cyclohexyl)oxy]tetrahydro-2H-pyranin Example 8, Step D. ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.03-1.31 (m,3 H) 1.35 (s, 12 H) 1.37-1.47 (m, 1 H) 1.47-1.64 (m, 4 H) 1.65-1.90 (m,3 H) 1.94 (dd, J=13.27, 2.93 Hz, 2 H) 2.04-2.15 (m, 2 H) 3.41-3.55 (m, 1H) 3.55-3.66 (m, 1 H) 3.76 (d, J=6.44 Hz, 2 H) 3.88-3.99 (m, 1 H)4.70-4.78 (m, 1 H) 6.55 (dd, 1 H) 6.67 (dd, J=8.39, 2.34 Hz, 1 H) 7.64(dd, J=8.29, 7.32 Hz, 1 H)

Step C)(2R)-4-[4-(2-fluoro-4-{[trans-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methoxy}phenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

The title compound (366 mg, 65.5 mmol) was prepared from(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-[(2R)-tetrahydro-2H-pyran-2-yloxy]butanamide(0.410 g, 8.23 mmol) and(+/−)-2-[(trans-4-{[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}cyclohexyl)oxy]tetrahydro-2H-pyran(0.358 g, 8.23 mmol) by a procedure analogous to that described for(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-{[cis-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methoxy}phenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamideExample 8, Step E. LCMS m/z 677.8 (M−1)

Step D) Preparation of(2R)-4-[4-{2-fluoro-4-[(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

The title (0.16 g, 62.6%) compound was prepared from(2R)-4-[4-(2-fluoro-4-{[trans-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methoxy}phenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(0.35 g, 0.516 mmol) by a procedure analogous to that described for(2R)-N-hydroxy-4-[4-{4-[(cis-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide,Example 8, Step F. LCMS m/z 511.7 (M+1) ¹H NMR (400 MHz, DMSO-d₆) δ ppm0.94-1.25 (m, 4 H) 1.57 (s, 3 H) 1.60-1.75 (m, 1 H) 1.83 (br. s., 4 H)2.08-2.24 (m, 1 H) 2.35-2.48 (m, 1 H) 3.11 (s, 3 H) 3.28-3.44 (m, 1 H)3.65-3.80 (m, 1 H) 3.84 (d, J=6.64 Hz, 2 H) 4.01-4.22 (m, 1 H) 6.47 (dt,J=7.18, 1.88 Hz, 1 H) 6.53 (s, 1 H) 6.87 (dd, J=8.79, 2.54 Hz, 1 H) 6.94(dd, J=13.38, 2.44 Hz, 1 H) 7.51 (t, J=8.98 Hz, 1 H) 7.71 (d, J=7.23 Hz,1 H) 9.24 (br. s., 1 H) 11.15 (s, 1 H)

Examples 10A-10N

The following compounds can be prepared by the procedures described inExample 6 through Example 10 where the appropriate alcohol or protectedderivative thereof is employed. Methods used to describe the synthesisof the precursor are analogously known to those skilled in the art.

TABLE 2 Example Retention Mass number IUPACNAME Time ion¹ Purity NMR10-A (2R)-N-hydroxy-4-[4-{4-[(4-hydroxy-4- Purity <80% 493 79 ¹H NMR(400 MHz, DMSO- methylcyclohexyl)oxy]phenyl}-2- UV-215 m/z d₆) d ppm1.10 (s, 3 H) oxopyridin-1(2H)-yl]-2-methyl-2- Impurity: 467.0 1.36-1.46(m, 2 H) 1.54 (s, 3 H) (methylsulfonyl)butanamide 0.46 1.57-1.62 (m, 2H) 1.68-1.76 (m, 2 H) 2.08-2.15 (m, 1 H) 2.32-2.40 (m, 1 H) 3.08 (s, 3H) 3.33-3.42 (m, 1 H) 3.66-3.75 (m, 1 H) 3.95-4.04 (m, 1 H) 4.04-4.13(m, 1 H) 4.27-4.36 (m, 1 H) 6.61 (s, 2 H) 7.00 (s, 2 H) 7.51-7.60 (m, 1H) 7.67-7.68 (m, 1 H) 7.69-7.75 (m, 1 H) 10-B(2R)-N-hydroxy-4-[4-{4-[(3-hydroxy-3- 0.46 479 90 1H NMR (CD3OD, 400MHz), methylcyclobutyl)methoxy]phenyl}-2- 7.65 (1H, d), 7.62 (1H, d),oxopyridin-1(2H)-yl]-2-methyl-2- 7.00 (1H, d), 6.74-6.72 (2H, m),(methylsulfonyl)butanamide 4.30-4.23 (1H, m), 4.00 (2H, d), 3.93-3.86(1H, m), 3.09 (3H, s), 2.59-2.51 (1H, m), 2.40-2.28 (2H, m), 2.18-2.13(2H, m), 1.99-1.93 (2H, m), 1.69 (3H, s), 1.36 (3H, s) ppm. 10-C(2R)-4-{4-[4-(3-cyanopropoxy)phenyl]-2- Purity <80% 448 77 1H NMR (400MHz, DMSO- oxopyridin-1(2H)-yl}-N-hydroxy-2- UV-215 m/z d6) d ppm 1.57(s, 3 H) methyl-2-(methylsulfonyl)butanamide Impurity: 279.1 2.00-2.09(m, J = 6.54, 6.54, 6.54, 0.45 6.54 Hz, 2 H) 2.17 (td, J = 12.20, 5.46Hz, 1 H) 2.42 (td, J = 12.44, 4.59 Hz, 1 H) 2.67 (t, J = 7.12 Hz, 2 H)3.11 (s, 3 H) 3.74 (dd, J = 11.42, 7.51 Hz, 1 H) 4.10 (t, J = 6.05 Hz, 4H) 6.60-6.67 (m, 2 H) 7.05 (d, J = 8.59 Hz, 2 H) 7.56 (dd, J = 7.22,3.71 Hz, 1 H) 7.58-7.66 (m, 1 H) 7.62 (d, J = 4.88 Hz, 1 H) 7.70 (d, J =8.59 Hz, 2 H) 10-D (2R)-N-hydroxy-4-[4-(4-{[3- 0.46 479 100 1H NMR (400MHz, DMSO- (hydroxymethyl)cyclobutyl]methoxy}phenyl)- d6) d ppm 1.56 (s,3 H) 2-oxopyridin-1(2H)-yl]-2-methyl-2- 1.75-1.92 (m, 2 H) 2.01-2.09 (m,1 (methylsulfonyl)butanamide H) 2.09-2.22 (m, 1 H) 2.24-2.45 (m, 2 H)2.52-2.69 (m, 1 H) 3.10 (s, 2 H) 3.37-3.46 (m, 1 H) 3.65-3.78 (m, 1 H)3.89-3.98 (m, 1 H) 4.02 (d, J = 0.78 Hz, 2 H) 4.05-4.16 (m, 1 H)4.38-4.54 (m, 1 H) 6.64 (s, 2 H) 7.01 (s, 2 H) 7.65 (s, 3 H) 9.14-9.32(m, 1 H) 10-E N-hydroxy-4-[4-{4-[(4-hydroxy-4- Purity <80% 481 80 ¹H NMR(400 MHz, methylpentyl)oxy]phenyl}-2-oxopyridin- UV-215 m/z METHANOL-d₄)d ppm 1(2H)-yl]-2-methyl-2- Impurity: 499.1 1.21 (s, 6 H) 1.60-1.69 (m,2 H) (methylsulfonyl)butanamide 0.45 1.70 (s, 3 H) 1.82-2.03 (m, 2 H)2.34-2.46 (m, 1 H) 2.60-2.74 (m, 1 H) 4.00-4.13 (m, 3 H) 4.31-4.44 (m, 1H) 6.97 (s, 1 H) 7.01-7.12 (m, 3 H) 7.71 (d, J = 8.79 Hz, 2 H) 7.89 (d,J = 7.03 Hz, 1 H) 10-F N-hydroxy-4-[4-(4-{[3- 0.41 465 100 ¹H NMR (400MHz, (hydroxymethyl)cyclobutyl]oxy}phenyl)- METHANOL-d₄) d ppm2-oxopyridin-1(2H)-yl]-2-methyl-2- 1.71 (s, 3 H) 2.20-2.55 (m, 7 H)(methylsulfonyl)butanamide 2.66-2.77 (m, 1 H) 3.07 (s, 3 H) 3.62 (d, J =6.44 Hz, 2 H) 4.07-4.19 (m, 1 H) 4.36-4.48 (m, 1 H) 4.76-4.84 (m, 1 H)6.95 (d, J = 8.59 Hz, 2 H) 7.05 (s, 1 H) 7.20 (d, J = 6.63 Hz, 1 H) 7.72(d, J = 8.78 Hz, 2 H) 7.98 (d, J = 6.83 Hz, 1 H) 10-G(2R)-N-hydroxy-4-[4-{4-[(4-hydroxy-4- 0.47 493 100 ¹H NMR (400 MHz,DMSO- methylcyclohexyl)oxy]phenyl}-2- d₆) d ppm 1.07 (br. s., 4 H)oxopyridin-1(2H)-yl]-2-methyl-2- 1.54 (s, 3 H) 1.59-1.70 (m,(methylsulfonyl)butanamide 1 H) 1.72-1.92 (m, 4 H) 2.05-2.24 (m, 1 H)2.31-2.43 (m, 1 H) 3.06 (s, 3 H) 3.23-3.41 (m, 1 H) 3.61-3.74 (m, 1 H)3.80 (s, 3 H) 4.01-4.16 (m, 1 H) 6.60 (ddd, 2 H) 6.97 (dd, 2 H)7.56-7.74 (m, 3 H) 11.16 (s, 1 H) 10-H(2R)-N-hydroxy-4-[4-(4-{[3-(1-hydroxy- 0.51 493 100 1H NMR (400 MHz,DMSO- 1-methylethyl)cyclobutyl]oxy}phenyl)-2- d6) d ppm 1.01 (s, 3 H)oxopyridin-1(2H)-yl]-2-methyl-2- 1.06 (s, 3 H) 1.56 (s, 3 H)(methylsulfonyl)butanamide 1.80-2.22 (m, 3 H) 2.23-2.48 (m, 3 H) 3.10(s, 3 H) 3.67-3.80 (m, 1 H) 4.04-4.15 (m, 1 H) 4.17-4.37 (m, 1 H)4.49-4.74 (m, 1 H) 6.55-6.70 (m, 2 H) 6.81-7.01 (m, 2 H) 7.56-7.78 (m, 3H) 10-I (2R)-4-[4-{3-fluoro-4-[(4-hydroxy-4- 0.48 511 100 1H NMR (CD3OD,400 HHZ), methylcyclohexyl)oxy]phenyl}-2- 7.77 (1H, d), 7.49-7.43 (2H,oxopyridin-1(2H)-yl]-N-hydroxy-2- m), 7.20 (1H, t),methyl-2-(methylsulfonyl)butanamide 6.74-6.70 (2H, m), 4.64-4.59 (1H,m), 4.31-4.23 (1H, m), 3.94-3.87 (1H, m), 3.09 (3H, s), 2.60-2.52 (1H,m), 2.39-2.32 (1H, m), 2.03-1.95 (2H, m), 1.81-1.74 (4H, m), 1.69 (3H,s), 1.54-1.48 (2H, m), 1.32-1.26 (1H, m), 1.24 (3H, s) ppm. 10-JN-hydroxy-4-{4-[4-(2-hydroxy-2- 0.4 453 100 ¹H NMR (400 MHz,methylpropoxy)phenyl]-2-oxopyridin- METHANOL-d₄) d ppm1(2H)-yl}-2-methyl-2- 1.32 (s, 6 H) 1.70 (s, 3 H)(methylsulfonyl)butanamide 2.32-2.47 (m, 1 H) 2.60-2.74 (m, 1 H) 3.08(s, 3 H) 3.85 (s, 2 H) 4.00-4.13 (m, 1 H) 4.31-4.45 (m, 1 H) 6.97 (s, 1H) 7.03-7.14 (m, 3 H) 7.72 (d, J = 8.79 Hz, 2 H) 7.89 (d, J = 6.83 Hz, 1H) 10-K (2R)-4-[4-{4-[(3,4-dihydroxy-4- 0.42 497 100 ¹H NMR (400 MHz,DMSO- methylpentyl)oxy]phenyl}-2-oxopyridin- d₆) d ppm 1.03 (s, 3 H)1.09 (s, 1(2H)-yl]-N-hydroxy-2-methyl-2- 3 H) 1.50-1.64 (m, 1 H)(methylsulfonyl)butanamide 1.57 (s, 3 H) 1.99-2.10 (m, 1 H) 2.12-2.22(m, 1 H) 2.36-2.46 (m, 1 H) 3.11 (s, 3 H) 3.27-3.41 (m, 2 H) 3.73 (td, J= 11.95, 4.59 Hz, 1 H) 4.04-4.20 (m, 3 H) 4.53 (br. s., 1 H) 6.61-6.67(m, 2 H) 7.02 (d, J = 8.78 Hz, 2 H) 7.65-7.74 (m, 3 H) 9.24 (br. s., 1H) 11.19 (s, 1 H) 10-L (2R)-4-[4-{2-fluoro-4-[(cis-4- 0.51 511 100 1HNMR (CD3OD, 400 HHZ), hydroxycyclohexyl)methoxy]phenyl}-2- 7.66 (1H, d),7.47 (1H, t), oxopyridin-1(2H)-yl]-N-hydroxy-2- 6.86 (1H, dd), 6.81 (1H,dd), methyl-2-(methylsulfonyl)butanamide 6.71 (1H, s), 6.64 (1H, d),4.33-4.25 (1H, m), 3.96-3.90 (2H, m), 3.87 (2H, d), 3.10 (3H, s),2.61-2.52 (1H, m), 2.41-2.32 (1H, m), 1.90-1.81 (1H, m), 1.78-1.72 (2H,m), 1.69 (3H, s), 1.65-1.55 (6H, m) ppm. Foot note ¹Mass Spec.- SeeMethod A as described in Table 5 infra.

Example 11(2R)-N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanamide

Step A) Ethyl2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoate

Ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate (25.02 g, 87.1 mmol)was added to a mixture of 4-phenylpyridin-2-ol (12.40 g, 72.43 mmol) andcesium carbonate (49.70 g, 152.5 mmol) in THF (150 mL). The reaction wasstirred and heated at 60° C. overnight. The reaction was diluted withethyl acetate (200 mL) and water (200 mL); the organics were separatedand the aqueous layer was extracted with ethyl acetate (2×150 mL). Thecombined organics were dried (MgSO₄), filtered, and concentrated toafford a crude solid. The crude was purified via flash chromatographyusing an Analogix SF65-400g column and eluted with ethyl acetate inheptane (30-80%) to afford the title compound as a white solid (16.79 g,61.4%). LC-MS m/z 378.6 (M+1). ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31(t, J=7.12 Hz, 3 H) 1.58 (s, 2 H) 2.41-2.62 (m, 2H) 3.09 (s, 3 H)3.90-4.01 (m, 1 H) 4.20-4.32 (m, 3 H) 6.40-6.45 (m, 1 H) 6.73 (d, J=1.56Hz, 1 H) 7.31 (d, J=7.03 Hz, 1 H) 7.37-7.46 (m, 2 H) 7.50-7.55 (m, 2 H).

Step B)(+/−)-2-Methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoic acid

(+/−)-Ethyl2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoatewas converted to the title product following the general procedureoutlined for(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid, Preparation 2B, Step B. The title compound was obtained as a whitesolid (69.83 g, 95.24%). LC-MS m/z 350.5 (M+1). ¹H NMR (400 MHz,DMSO-d₆) δ ppm 1.57 (s, 3 H) 2.13-2.24 (m, 1 H) 2.39-2.47 (m, 1 H) 3.17(s, 3 H) 3.83-3.99 (m, 1 H) 4.02-4.16 (m, 1 H) 6.59-6.63 (m, 1 H) 6.66(d, J=1.76 Hz, 1 H) 7.35-7.56 (m, 3 H) 7.64-7.87 (m, 3 H) 13.87 (br. s.,1 H).

Step C) Chiral separation to provide(2R)-2-Methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoicacid

(+/−)-2-Methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoicacid (69.83 g) was dissolved in methylene chloride/ethanol (2 L) andresolved using an Analytical SFC-4 instrument, AS-H column (30×250), aCO2/Propanol (85/15) mobile phase with isopropylamine as the modifier,with a flow rate of 128g/min to afford enantiomer 1 (22.5 g, rt=3.09min, [α]₅₈₉ ²⁰=+35.96°) at 96.46% enantiomeric purity and enantiomer 2(26.63 g, rt=4.18 min) at 98.48% enantiomeric purity. It was determinedthat enantiomer 2 was the title compound

Step D) Preparation of(2R)-2-Methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-2-Methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoicacid was converted to the title product following the general procedureoutlined for4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidePreparation 2 A, Step D, using N,N-diisopropylethylamine in place oftriethylamine. The title compound was obtained as a white solid (5.15 g,80.24%) LC-MS m/z 449.7 (M+1).

Step E)(2R)-N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanamide

HCl (4.0 N in 1,4-dioxane, 20 mL) was added to a solution of(2R)-2-Methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(5.15 g, 11.5 mmol) in 1,4-dioxane (100 mL) and water (20 mL). Thereaction was continued for 2 hours. The reaction was concentrated invacuo, upon concentration a white solid precipitated. The solid wastriturated with 2-propanol (150 mL) at 50° C. for 30 minutes thencollected by filtration. The title compound was obtained as a whitesolid (3.85 g, 92%) LC-MS m/z 365.5 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δppm 1.58 (s, 3 H) 2.10-2.23 (m, 1 H) 2.37-2.48 (m, 1 H) 3.11 (s, 3 H)3.69-3.82 (m, 1 H) 4.04-4.19 (m, 1 H) 6.63-6.68 (m, 1 H) 6.70 (d, J=1.76Hz, 1 H) 7.41-7.55 (m, 3 H) 7.68-7.75 (m, 2 H) 7.77 (d, J=6.83 Hz, 1 H)11.17 (br. s., 1 H). [α]₅₈₉ ²⁰=+33.21°.

Example 12(2R)-4-[4-(2-fluoro-4-hydroxy-3-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A) 2-(4-bromo-3-fluorophenoxy)tetrahydro-2H-pyran

Pyridinium p-toluene sulfonic acid (789 mg, 3.1 mmol) was added to asolution of 4-bromo-3-fluorophenol (4.00 g, 20.9 mmol) and3,4-dihydro-2H-pyran (3.52 g, 41.9 mmol) in dichloromethane (105 mL,0.2M). After 2h the reaction was quenched with saturated aqueous sodiumbicarbonate and the layers were separated. The aqueous layer wasextracted with dichloromethane (2×). The organic layers were combined,dried (Na₂SO₄), filtered and concentrated to give a colorless oil. Thematerial was loaded onto a 25g silica guard column and run on a 330gcolumn with 0-5% EtOAc in heptane. Desired material was concentrateddown yielding 1900 mg (33%) of a clear colorless oil.

¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.56-1.77 (m, 3 H) 1.82-1.89 (m, 2H) 1.89-2.07 (m, 1 H) 3.62 (m, J=11.37, 4.07, 4.07, 1.37 Hz, 1 H) 3.85(ddd, J=11.32, 10.05, 3.02 Hz, 1 H) 5.38 (dd, J=3.12 Hz, 1 H) 6.76 (ddd,J=8.88, 2.73, 1.07 Hz, 1 H) 6.89 (dd, J=10.34, 2.73 Hz, 1 H) 7.35-7.46(m, 1 H).

Step B) 2-(4-bromo-3-fluoro-2-methylphenoxy)tetrahydro-2H-pyran

2-(4-bromo-3-fluorophenoxy)tetrahydro-2H-pyran (1200 mg, 4.4 mmol) wasdissolved in tetrahydrofuran (22 mL, 0.2M) under nitrogen and cooled to−78° C. To this was added (600 mg, 5.6 mmol) lithium diisopropylamide insolution dropwise over 5 minutes. The reaction mixture was stirred for 1h at −78° C. Methyl iodide (948 mg, 6.5 mmol) was then added dropwise.The reaction was stirred at −78° C. for 30 min and allowed to warm to RTovernight. The mixture was quenched with water and 10 mL of saturatedaqueous ammonium chloride solution. The reaction was extracted withdiethyl ether (3×). The organic layer was dried over sodium sulfate,filtered and evaporated to yield 1.17 g (93%) of a light yellow mix ofsolid and oil. ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.57-1.78 (m, 3 H)1.85-1.93 (m, 2 H) 1.95-2.08 (m, 1 H) 2.21 (d, J=2.34 Hz, 3H) 3.61 (m,J=11.27, 3.98, 3.98, 1.46 Hz, 1 H) 3.78-3.88 (m, 1 H) 5.41 (t, J=3.12Hz, 1 H) 6.81 (dd, J=8.98, 1.37 Hz, 1 H) 7.27 (d, J=16.98 Hz, 1 H)

Step C)2-[3-fluoro-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]tetrahydro-2H-pyran

Potassium acetate (810 mg, 8.1 mmol) was added to a suspension of2-(4-bromo-3-fluoro-2-methylphenoxy)tetrahydro-2H-pyran (1170 mg, 4.0mmol) in p-dioxane (41 mL, 0.1M). After 10 minutes,bis(pinacolato)diborane (1230 mg, 4.9 mmol) and dichloro1,1′-bis(diphenylphosphino)ferrocene palladium(II) (96 mg, 0.13 mmol)were added. The resulting suspension was heated to 100° C. 18h. Anadditional 100 mg of catalyst was added. After another 24h, anadditional 100 mg of catalyst was added. After another 24h (66h total)the material was filtered through celite, concentrated and loaded onto a120g silica column (0-10% ethyl acetate in hexanes). The product wasconcentrated to yield 677 mg (50%) as a golden brown oil. Contains somebis(pinacolato)diborane impurity. Partial NMR ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 1.56-1.78 (m, 3 H) 1.82-1.95 (m, 2 H)1.96-2.07 (m, 1 H) 2.16 (d, J=2.15 Hz, 3 H) 3.57-3.68 (m, 1 H) 3.70-3.92(m, 1 H) 5.50 (t, J=2.93 Hz, 1 H) 6.88 (d, J=8.39 Hz, 1 H) 7.51 (t,J=7.71 Hz, 1 H)

Step D)(2R)-4-{4-[2-fluoro-3-methyl-4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Pd EnCat™ (150 mg, 0.05 mmol) was added to a mixture of potassiumcarbonate (370 mg, 2.7 mmol) the2-[3-fluoro-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]tetrahydro-2H-pyran(150 mg, 0.45 mmol) and(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2B, Step C, (267 mg, 0.54 mmol)in 1,4-dioxane (3.5 mL, 0.1M) and water (0.5 mL). The resultingsuspension was heated to 100° C. and left to stir 66h. The material wascooled, filtered through celite and concentrated yielding 256 mg (99%TY) of white solid. LCMS m/z 579.8 (M−1) Partial NMR capturing aromaticand dietheric THP protons. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.97 (br. s.,1 H) 5.58-5.64 (m, 1 H) 6.46 (dt, J=7.02, 1.85 Hz, 1 H) 6.52 (s, 1 H)7.01 (d, J=8.78 Hz, 1 H) 7.36 (t, J=8.98 Hz, 1 H) 7.68 (d, J=7.02 Hz, 1H)

Step E) (2R)-4-[4-(2-fluoro-4-hydroxy-3-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

(2R)-4-{4-[2-fluoro-3-methyl-4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(335 mg, 0.58 mmol) was dissolved in 3 mL of dioxane. To this solutionwas added 1 mL of 4M HCl in dioxane 1 mL of water. The resultingsolution was stirred at RT for 10 minutes. The material was diluted upwith methanol and concentrated (3×). Dichloromethane was added and themixture was stirred for 18 h. The solution retained color and a fineparticulate was suspended. The mixture was filtered leaving 13.3 mg (6%)of white solid. LCMS m/z 413.6 (M+1) ¹H NMR (400 MHz, METHANOL-d₄) δ ppm1.71 (s, 3 H) 2.14 (d, J=1.56 Hz, 3 H) 2.33-2.46 (m, 1 H) 2.54-2.68 (m,1 H) 3.10 (s, 3 H) 3.91-4.05 (m, 1 H) 4.24-4.40 (m, 1 H) 6.70 (d, J=8.59Hz, 1 H) 6.75-6.86 (m, 2 H) 7.23 (t, J=8.68 Hz, 1 H) 7.75 (d, J=6.83 Hz,1 H)

Example 13(2R)-4-[4-(2-fluoro-4-methylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Pd EnCat™ (0.1 eq) was added to a mixture of potassium carbonate (3.0eq), (2-fluoro-4-methylphenyl)boronic acid (201 mg, 1.3 mmol) and(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2B (1.0 eq) in dioxane:water(0.1 M, 5:1 mixture). The reaction mixture was heated overnight at 80°C. The reaction was cooled to ambient temperature and filtered throughcelite and eluted with ethyl acetate. The filtrate was concentrated invacuo, then subjected to the standard THP-deprotection step as describedfor the formation of(2R)-4-[4-(2-fluoro-4-hydroxy-3-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamidein Example 12, Step E. LCMS m/z 397.6 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δppm 1.58 (s, 3 H) 2.17 (td, J=12.20, 5.07 Hz, 1 H) 2.36 (s, 3 H) 2.44(td, J=12.15, 4.98 Hz, 1 H) 3.11 (s, 3 H) 3.75 (td, J=12.00, 4.68 Hz, 1H) 4.12 (td, J=11.90, 5.07 Hz, 1 H) 6.43-6.52 (m, 1 H) 6.56 (s, 1 H)7.05-7.24 (m, 2 H) 7.47 (t, J=8.10 Hz, 1 H) 7.73 (d, J=7.02 Hz, 1 H)9.25 (br. s., 1 H) 11.14 (s, 1 H)

Example 14(2R)-4-[4-(2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Title compound was prepared using (2,3-difluorophenyl)boronic acid (114mg, 0.72 mmol) following the general methodology of Example 13. Yield 99mg (41%) of yellow solid. LCMS m/z 401.5 (M+1). ¹H NMR (400 MHz,DMSO-d₆) δ ppm 1.58 (s, 3 H) 2.18 (td, J=12.20, 4.88 Hz, 1 H) 2.38-2.48(m, 1 H) 3.11 (s, 3 H) 3.77 (td, J=12.00, 4.88 Hz, 1 H) 4.13 (td,J=11.90, 5.07 Hz, 1 H) 6.50 (dt, J=7.02, 1.85 Hz, 1 H) 6.61 (s, 1 H)7.28-7.37 (m, 1 H) 7.37-7.44 (m, 1 H) 7.54 (m, J=10.17, 8.13, 8.13, 1.66Hz, 1 H) 7.79 (d, J=7.02 Hz, 1 H) 9.25 (s, 1 H) 11.12 (s, 1 H)

Example 15(2R)-4-[4-(4-chlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Title compound was prepared using (4-chlorophenyl)boronic acid (113 mg,0.72 mmol) following the general methodology of Example 13. The productwas purified using 35-50% acetonitrile in water. Yield 112 mg (47%) ofyellow solid. LCMS m/z 399.5 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.57(s, 3 H) 2.09-2.23 (m, 1 H) 2.38-2.48 (m, 1 H) 3.11 (s, 3 H) 3.75 (td,J=11.95, 4.78 Hz, 1 H) 4.12 (td, J=11.81, 5.07 Hz, 1 H) 6.65 (dd,J=7.12, 2.05 Hz, 1 H) 6.72 (d, J=1.95 Hz, 1 H) 7.52-7.57 (m, 2 H)7.72-7.80 (m, 3 H) 9.24 (br. s., 1 H) 11.14 (s, 1 H)

Example 16(2R)-N-hydroxy-2-methyl-4-[4-(4-methylphenyl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide

Title compound was prepared using (4-methylphenyl)boronic acid (98 mg,0.72 mmol) following the general methodology of Example 13. Yield 79 mg(35%) of yellow solid. LCMS m/z 379.6 (M+1) ¹H NMR (400 MHz, DMSO-d₆) δppm 1.57 (s, 3 H) 2.11-2.22 (m, 1 H) 2.35 (s, 3 H) 2.37-2.47 (m, 1 H)3.11 (s, 3 H) 3.74 (td, J=11.95, 4.78 Hz, 1 H) 4.11 (td, J=11.90, 5.07Hz, 1 H) 6.64 (dd, J=7.12, 2.05 Hz, 1 H) 6.68 (d, J=1.76 Hz, 1 H) 7.30(d, J=8.20 Hz, 2 H) 7.62 (d, J=8.00 Hz, 2 H) 7.73 (d, J=7.02 Hz, 1 H)9.24 (br. s., 1H) 11.17 (s, 1 H)

Example 17(2R)-N-hydroxy-4-[4-(4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

Title compound was prepared from (4-methoxyphenyl)boronic acid (110 mg,0.72 mmol) using the general methodology of Example 13. Yield 35 mg(15%) of yellow solid. LCMS m/z 395.6 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δppm 1.57 (s, 3 H) 2.11-2.23 (m, 1 H) 2.35-2.47 (m, 1 H) 3.11 (s, 3 H)3.68-3.79 (m, 1 H) 3.81 (s, 3 H) 4.10 (td, J=11.85, 5.17 Hz, 1 H)6.60-6.68 (m, 2 H) 7.03 (d, J=8.98 Hz, 2 H) 7.60-7.76 (m, 3 H) 9.25 (s,1 H) 11.18 (s, 1 H)

Example 18(2R)-4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A)(2R)-4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Pd EnCat™ (200 mg, 0.6 mmol) was added to a mixture of potassiumcarbonate (250 mg, 1.8 mmol), 2,3-dihydro-1,4-benzodioxin-6-ylboronicacid (130 mg, 0.72 mmol), and(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2B, Step C, (300 mg, 0.6 mmol)in dioxane:water (5 mL, 5:1mixture). The reaction mixture was heatedovernight at 80° C. The reaction was cooled to ambient temperature,filtered through celite and washed with ethyl acetate. The crudematerial was concentrated and loaded onto a 12g silica column and runusing 0-100% ethyl acetate in hexanes. (Some material was lost duringpurification). The material was concentrated yielding 44 mg (15%) of alight yellow glass. LCMS m/z 505.7 (M−1)

Step B)(2R)-4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

(2R)-4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(581 mg, 1 mmol) was dissolved in 3 mL of dichloromethane. To thissolution was added 1 mL of 4M HCl in dioxane 1 mL of water. The reactionwas monitored for completion by LCMS. After standing overnight, a solidprecipitated. The solid was collected by filteration and dried in vacuoyielding 25 mg (68%) of light yellow solid. LCMS m/z 423.5 (M+1) 1H NMR(400 MHz, DMSO-d₆) δ ppm 1.57 (s, 3 H) 2.09-2.22 (m, 1 H) 2.36-2.46 (m,1 H) 3.10 (s, 3 H) 3.65-3.79 (m, 1 H) 4.03-4.15 (m, 1 H) 4.28 (s, 4 H)6.59-6.66 (m, 2 H) 6.94 (d, J=8.20 Hz, 1 H) 7.19-7.26 (m, 2 H) 7.67-7.73(m, 1 H)

Example 19(2R)-N-hydroxy-2-methyl-4-[4-(2-methyl-1H-indol-5-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide

Step A)(2R)-N-hydroxy-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanamide

(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2B, Step C (300 mg, 0.6 mmol)was dissolved in 3 mL of p-dioxane. To this solution was added 1 mL ofwater and 0.5 mL of 4M HCl in water. The reaction was monitored forcompletion by LCMS. Upon completion (10 minutes), the reaction mixturewas concentrated and recrystallized from methanol. 115 mg (46%) of whitesolid was isolated by filtration. LCMS m/z 415.3 (M+1). 1H NMR (400 MHz,DMSO-d₆) δ ppm 1.54 (s, 3 H) 2.04-2.14 (m, 1 H) 2.34-2.44 (m, 1 H) 3.08(s, 3 H) 3.62-3.72 (m, 1 H) 3.96-4.06 (m, 1 H) 6.62 (dd, J=7.13, 1.86Hz, 1 H) 6.94 (d, J=1.76 Hz, 1 H) 7.44 (d, J=7.03 Hz, 1 H) 9.23 (br. s.,1 H) 11.04 (s, 1 H)

Step B)2-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

Potassium acetate (477 mg, 4.76 mmol) was added to a solution of5-bromo-2-methylindole (500 mg, 2.4 mmol), bis(pinacolato)diboron (725mg, 2.86 mmol), and[1,1′-bis-(diphenylphosphino)ferrocene]-dichloropalladium(II) dcmcomplex (178 mg, 0.24 mmol) in 1,4-dioxane (25 mL) in a 20 mL vial. Thevial was capped and heated to 80° C., reaction was heated at thistemperature with stirring overnight.

The reaction mixture was concentrated, dissolved in EtOAc, and filteredthrough a 5g silica plug. This filtrate was concentrated and purified onan 80g silica column using 0-10% ethyl acetate in hexanes to furnish 202mg (33%) of a clear colorless oil. LCMS m/z 258.3 (M+1) 1H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.39 (s, 21 H) 2.40 (s, 3 H) 6.24 (s, 1 H) 7.25 (d,J=8.20 Hz, 1 H) 7.60 (d, J=8.20 Hz, 1 H) 7.94 (br. s., 1 H) 8.08 (s, 1H)

Step C)(2R)-N-hydroxy-2-methyl-4-[4-(2-methyl-1H-indol-5-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide

Pd EnCat™ (93 mg, 0.03 mmol) was added to a mixture of potassiumcarbonate (115 mg, 0.83 mmol),2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (86mg, 0.33 mmol), and(2R)-N-hydroxy-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanamide(115 mg, 0.28 mmol) in dioxane:water (2.5 mL, 5:1 mixture). The reactionmixture was heated overnight at 80° C. The reaction was cooled toambient temperature, filtered through a nylon filter and concentrated.The material was dissolved in a minimal amount of DMSO and loaded onto a13g c18 column. The gradient was run from 25-45% acetonitrile in water.The desired material was concentrated yielding 25 mg (22%) of a lightbrown solid. LCMS m/z 418.5 (M+1) 1H NMR (400 MHz, DMSO-d₆) δ ppm 1.58(s, 3 H) 2.13-2.24 (m, 1 H) 2.32-2.46 (m, 1 H) 2.39 (s, 3 H) 3.12 (s, 3H) 3.69-3.78 (m, 1 H) 4.06-4.16 (m, 1 H) 6.20 (s, 1 H) 6.65 (d, J=1.95Hz, 1 H) 6.70 (dd, J=7.22, 1.95 Hz, 1 H) 7.31-7.39 (m, 2 H) 7.70 (d,J=7.22 Hz, 1 H) 7.79 (s, 1 H) 9.25 (br. s., 1 H) 11.11 (br. s., 1 H)11.23 (br. s., 1 H)

Example 20(2R)-4-[4-(4-chloro-2-fluorophenyl)-2-oxopridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A)(2R)-4-[4-(4-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Pd EnCat™ (333 mg, 0.1 mmol) was added to a mixture of potassiumcarbonate (832 mg, 6.0 mmol), (2-fluoro-4-chlorophenyl)boronic acid (227mg, 1.3 mmol), and(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2B, Step C (500 mg, 1.0 mmol) indioxane:water (8 mL, 5:1mixture). The reaction mixture was heatedovernight at 80° C. The reaction was cooled to ambient temperature,filtered through celite and washed with ethyl acetate. The crudematerial was concentrated yielding 1188 mg (236%) of impure light yellowsolid. LCMS m/z 499.7 (M−1)

Step B)(2R)-4-[4-(4-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

(2R)-4-[4-(4-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(1188 mg impure material, 1 mmol) was dissolved in 3 mL ofdichloromethane. To this solution was added 1 mL of 4M HCl in dioxaneand 1 mL of water. The reaction was monitored for completion by LCMS.Upon completion, the reaction mixture was concentrated and redissolvedin a minimal amount of dimethylsulfoxide and water and loaded onto a 5gc18 guard-column. This material was purified on a 75g c18 column with10-40% acetonitrile in water with 0.1% trifluoroacetic acid. The desiredmaterial was concentrated yielding 434 mg (88%) of a light yellow solid.LCMS m/z 417.5 (M+1). 1H NMR (400 MHz, DMSO-d₆) δ ppm 1.58 (s, 3 H)2.10-2.23 (m, 1 H) 2.37-2.47 (m, 1 H) 3.11 (s, 3 H) 3.69-3.82 (m, 1 H)4.04-4.19 (m, 1 H) 6.44-6.52 (m, 1 H) 6.58 (s, 1 H) 7.42 (dd, J=8.29,1.85 Hz, 1 H) 7.56-7.67 (m, 2 H) 7.77 (d, J=7.02 Hz, 1 H) 11.12 (br. s.,1 H)

Example 21(2R)-4-[4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A:(2R)-4-[4-(2-Fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoicacid

(2-Fluoro-4-methoxyphenyl)boronic acid (3.89 g, 22.43 mmol), ethyl(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate(7.68 g, 17.98 mmol), (which may be produced as in the preparation of 2Acompound IV Step B except that (R)-ethyl4-bromo-2-methyl-2-(methylsulfonyl)butanoate was used), and Pd(dppf)Cl₂;DCM complex (0.60 g, 0.73 mmol) were charged into a round bottom flask,flushed with nitrogen, and dissolved in methyltetrahydrofuran (75 mL).Potassium phosphate, tribasic (11.45 g, 53.94 mmol) in water (37 mL) wasadded to the flask and the reaction was heated to 65° C. for 45 minutes.The reaction was allowed to cool and the aqueous layer was separated.The organics were transferred back in the flask and lithium hydroxide(1.31 g, 53.88 mmol) in water (25 mL) was added to the organics and themixture was heated to 55° C. for 1 hour. The mixture was allowed to cooland the aqueous layer was separated. The organics were extracted with 1Naqueous sodium hydroxide (2×25 mL). The combined aqueous layers werewashed with ethyl acetate (3×25 mL), treated with celite (3 g) andfiltered. The filter pad was washed with water (25 mL) and the combinedfiltrates were treated dropwise with 6N aqueous HCl to afford a pH of 3and a cream colored precipitate. The solid was collected via filtrationand dried under vacuum to afford the title compound as a tan solid (6.50g, 90.99%). HPLC/MS m/z 398 (M+1)

¹H NMR (d-6-DMSO) δ 7.70 (d, J=7.43 Hz, 1H), 7.51 (t, J=9.37 Hz, 1H),6.95 (dd, J=13.27, 2.34 Hz, 1H), 6.87 (dd, J=8.59, 2.73 Hz, 1H), 6.49(s, 1H), 6.95 (dt, J=6.42, 1.95 Hz, 1H), 4.10-4.02 (m, 1H), 3.94-3.84(m, 1H), 2.46-2.37 (m, 1H), 2.22-2.13 (m, 1H), 1.55 (s, 3H).

Step B:(2R)-4-[4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-[4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoicacid (2.38 g, 5.99 mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (1.38g, 7.86 mmol) were charged into a round bottom flask, flushed withnitrogen, and dissolved in 2-methyltetrahydrofuran (20 mL). The mixturewas treated with N-methylmorpholine (0.92 mL, 8.39 mmol) and stirred for85 minutes. THP-hydroxylamine (0.94 g, 8.07 mmol) in MeTHF (3.0 mL) wasadded dropwise via syringe and the reaction was stirred for 45 minutes.The aqueous layer was separated and extracted with MeTHF (20 mL). Thecombined organics were washed with brine (15 mL), dried (Na₂SO₄),filtered, and concentrated to afford the title compound as a solid glass(3.67 g) which contains impurities. LCMS m/z 495.7 (M−1) Used as is inthe next step.

Step C:(2R)-4-[4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

(2R)-4-[4-(2-Fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(34.7 mg, 69.9 mmol) and pyridinium p-toluenesulfonic acid (8.8 mg, 34.9mmol) were dissolved in ethanol (277.6 uL) and immersed in a 75° C. oilbath. The reaction was stirred at this temperature for 1 hour andallowed to cool. Water (600 uL) was added to the solution and thereaction was stirred overnight. A solid was collected via filtration anddried under vacuum to afford the title compound as an off-white powder(22 mg, 76.33%). LCMS m/z 413.5 (M+1). 1H NMR (400 MHz, DMSO-d₆) δ ppm1.57 (s, 3 H) 2.11-2.22 (m, 1 H) 2.37-2.47 (m, 1 H) 3.10 (s, 3 H)3.68-3.79 (m, 1 H) 3.82 (s, 3 H) 4.05-4.16 (m, 1 H) 6.44-6.50 (m, 1 H)6.54 (s, 1 H) 6.89 (dd, J=8.68, 2.44 Hz, 1 H) 6.97 (dd, J=13.37, 2.44Hz, 1 H) 7.54 (dd, J=8.98, 8.98 Hz, 1 H) 7.71 (d, J=7.02 Hz, 1 H) 11.14(br. s., 1 H).

Example 22(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2,3,6-trifluorophenyl)pyridin-1(2H)-yl]butanamide

Step A)(2R)—N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2,3,6-trifluorophenyl)pyridin-1(2H)-yl]butanamide

To an 8 mL tube was added 0.15 mmol of 2-bromo-1,3,4-trifluorobenzene(32 mg), a 1.0 mL DMF solution of(2R)-4-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 3 (73 mg, 0.15 mmol), a 0.10 mLaqueous solution of K₂CO₃ (62 mg, 0.45 mmol), and Pd EnCat™ (75 mg). Theresulting suspension was shaken at 80° C. for 14 hr. Completeconsumption of starting material was confirmed by LCMS, with the majorpeak confirmed as desired coupling product by ionization. The mixturewas then diluted with 2 mL dioxane and 350 mg celite was added. Theresulting mixture was shaken at room temperature for 15 min and thenfiltered. To the filtrate was added 0.5 mL 1 N HCl (aq.) and resultingmixture shaken at room temperature for 4 hrs. The reaction mixture wasthen concentrated in the Genevac. The residue was then dissolved in 2 mLDMSO, filtered and purified using a Sunfire C18 ODB 5u 19×100 mm column,1 to 60% ACN in water with 0.01% TFA at 22 mL/min flow rate over a 12min run time. Pure desired product was obtained, 10 mg off white solid(16%). LCMS m/z 419.2 (M+H), 837.3 (2M+H); 1H NMR (400 MHz, DMSO-d6) dppm 1.54 (s, 3 H) 2.14 (td, J=12.26, 5.18 Hz, 1 H) 2.39-2.44 (m, 1 H)2.46 (s, 3 H) 3.72 (td, J=12.01, 4.88 Hz, 1 H) 4.09 (td, J=11.96, 4.79Hz, 1 H) 6.37 (d, J=7.03 Hz, 1 H) 6.54 (s, 1 H) 7.27 (t, J=9.18 Hz, 1 H)7.59 (qd, J=9.38, 4.88 Hz, 1 H) 7.77 (d, J=7.03 Hz, 1 H) 11.08 (br. s.,1 H).

Example 23(2R)-N-hydroxy-2-methyl-4-{4-[4-(2-methylpyrimidin-4-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide

Example 23 was carried out using the general methodology described inExample 22. Title compound was made from the corresponding bromide (0.15mmol): 4-(4-bromophenyl)-2-methylpyrimidine. Product isolated is an offwhite solid, 21 mg (31%). LCMS m/z 457.3 (M+1); 1H NMR (400 MHz,DMSO-d6) d ppm 0.94 (s, 3 H) 1.59 (ddd, J=13.23, 11.18, 5.08 Hz, 1 H)1.81 (ddd, J=13.23, 11.18, 5.08 Hz, 1 H) 2.07 (s, 3 H) 2.41 (s, 3 H)3.10-3.21 (m, 1 H) 3.52 (ddd, J=12.55, 11.08, 5.27 Hz, 1 H) 6.07 (dd,J=7.13, 2.05 Hz, 1 H) 6.14 (d, J=2.15 Hz, 1 H) 7.08 (d, J=7.23 Hz, 1 H)7.20 (m, J=8.79 Hz, 2 H) 7.32 (d, J=5.66 Hz, 1 H) 7.64 (m, J=8.79 Hz, 2H) 8.12 (d, J=5.66 Hz, 1 H).

Example 24(2R)-N-hydroxy-2-methyl-4-{4-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide

Example 24 was carried out using the general methodology described inExample 22. Title compound was made from the corresponding bromide (0.15mmol): 5-(4-bromophenyl)-1-methyl-1H-pyrazole. Product isolated is anoff white solid, 11 mg (16%). LCMS m/z 445.3 (M+1); 1H NMR (400 MHz,DMSO-d6) d ppm 0.94 (s, 3 H) 1.58 (ddd, J=13.23, 11.38, 5.47 Hz, 1 H)1.75-1.84 (m, 1 H) 2.41 (s, 3 H) 3.14 (td, J=12.01, 4.69 Hz, 1 H) 3.21(s, 3 H) 3.45-3.58 (m, 1 H) 6.02 (d, J=2.15 Hz, 1 H) 6.04 (dd, J=7.13,2.05 Hz, 1 H) 6.08 (d, J=1.95 Hz, 1 H) 6.97 (d, J=2.15 Hz, 1 H)7.02-7.07 (m, 3 H) 7.20 (d, J=8.59 Hz, 2 H).

Example 25(2R)-N-hydroxy-2-methyl-4-{4-[4-(2-methyl-1,3-oxazol-4-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide

Example 25 was carried out using the general methodology described inExample 22. Title compound was made from the corresponding bromide (0.15mmol): 4-(4-bromophenyl)-2-methyloxazole. Product isolated is an offwhite solid, 7 mg (10%). LCMS m/z 446.1 (M+1); 1H NMR (400 MHz, DMSO-d6)d ppm 1.55 (s, 3 H) 2.14 (td, J=12.21, 5.08 Hz, 1 H) 2.34-2.45 (m, 1 H)2.65 (s, 3 H) 3.08 (s, 3 H) 3.73 (td, J=11.91, 4.69 Hz, 1 H) 4.09 (td,J=11.91, 5.08 Hz, 1 H) 6.68 (dd, J=7.23, 2.15 Hz, 1 H) 6.76 (d, J=2.15Hz, 1 H) 7.77 (d, J=7.03 Hz, 1 H) 7.85-7.92 (m, 2 H) 8.02-8.08 (m, 2 H)9.18-9.31 (m, 1 H) 11.13 (s, 1 H).

Example 26(2R)-N-hydroxy-2-methyl-4-{4-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide

Example 26 was carried out using the general methodology described inExample 22. Title compound was made from the corresponding bromide (0.15mmol): 3-(4-bromophenyl)-5-methyl-1,2,4-oxadiazole. Product isolated isa white solid, 14 mg (17%). LCMS m/z 447.2; 1H NMR (400 MHz, DMSO-d6) dppm 1.58 (s, 3 H) 2.11-2.25 (m, 1 H) 2.37-2.48 (m, 1 H) 2.68 (s, 3 H)3.12 (s, 3 H) 3.44 (br. s., 1 H) 3.76 (td, J=11.91, 4.69 Hz, 1 H) 4.13(td, J=11.91, 5.08 Hz, 1 H) 6.72 (dd, J=7.23, 2.15 Hz, 1 H) 6.79 (d,J=2.15 Hz, 1 H) 7.81 (d, J=7.03 Hz, 1 H) 7.92 (d, J=8.59 Hz, 2 H) 8.08(d, J=8.59 Hz, 2 H) 9.29 (br. s., 1 H) 11.17 (s, 1 H).

Example 27(2R)-N-hydroxy-2-methyl-4-{4-[4-(2-methylpyrimidin-5-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide

Example 27 was carried out using the general methodology described inExample 22. Title compound was made from the corresponding bromide (0.15mmol): 5-(4-bromophenyl)-2-methylpyrimidine. Product isolated is an offwhite solid, 19 mg (28%). LCMS m/z 457.2 (M+1); 1H NMR (400 MHz,DMSO-d₆) d ppm 1.58 (s, 3 H) 2.13-2.24 (m, 1 H) 2.39-2.48 (m, 1 H) 2.68(s, 3 H) 3.12 (s, 3 H) 3.76 (td, J=12.06, 4.79 Hz, 1 H) 4.13 (td,J=11.91, 4.88 Hz, 1 H) 6.74 (dd, J=7.13, 2.05 Hz, 1 H) 6.80 (d, J=2.15Hz, 1 H) 7.79 (d, J=7.03 Hz, 1 H) 7.85-7.96 (m, 4 H) 9.10 (s, 2 H).

Example 28(2R)-4-{4-[4-(difluoromethoxy)-2-fluorophenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A) 1-Bromo-4-difluoromethoxy-2-fluoro-benzene

To a solution of 4-bromo-3-fluoro-phenol (962 mg, 5.037 mmol) inacetonitrile (25 mL) was added a solution of potassium carbonate (28.3g, 181 mmol) dissolved in water (25 mL) all under nitrogen. To thereaction mixture was added 2-chloro-2,2-difluoroacetophenone (5 g, 25mmol) and the reaction was heated to 80° C. for 4 hours. The reactionwas cooled to room temperature and extracted with ethyl acetate (3×50mL). The organic layer was dried with sodium sulfate, filtered andconcentrated onto silica gel. Silica gel chromotography (5% ethylacetate 95% heptane to 100% ethyl acetate over 55 minutes) furnished aclear oil (950 mg, 78%). LCMS m/z 531.7 (M−1) ¹H NMR (400 MHz,METHANOL-d₄) δ ppm 6.85 (s, 1 H) 6.92 (dd, J=8.88, 2.63 Hz, 1 H) 7.05(t, 1 H) 7.38 (t, 1 H)

Step B)(2R)-4-{4-[4-(difluoromethoxy)-2-fluorophenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-(4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 3 (240 mg, 0.495 mmol),1-bromo-4-difluoromethoxy-2-fluoro-benzene, (159 mg, 0.990 mmol),potassium carbonate (274 mg, 1.98 mmol), and dioxane (3 mL) were addedto a 5 mL microwave vial with a stir bar, followed by the addition ofwater (0.30 mL) and Pd II Encat (128 mg, 0.050 mmol). The reaction wasirradiated at 120° C. for 45 minutes in a microwave reactor. Thereaction was filtered through a thin film of celite, rinsed with ethylacetate then concentrated. Purification via silica gel chromatography(15% ethyl acetate 85% heptane to 100% ethyl acetate over 45 minutes)and then (5% MeOH 95% ethyl acetate for an additional 5 minutes)afforded the product as a white solid (120 mg, 45%). LC-MS m/z 531.7(M−1).

Step C)(2R)-4-{4-[4-(difluoromethoxy)-2-fluorophenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

To a stirred solution of(2R)-4-{4-[4-(difluoromethoxy)-2-fluorophenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(120 mg, 0.225 mmol) in DCM (3 mL) was added a solution of 4M hydrogenchloride in dioxane (1.7 mL, 6.75 mmol). After 30 minutes the reactionwas quenched through the addition of methanol 0.5 mL. The reaction wasconcentrated then purified via reverse phase chromatography (Method: 95%water/5% methanol (initial conditions) linear gradient to 5% water/95%methanol for 10.0 min, then HOLD 0% water/100% methanol for 1.0 min.Flow rate, 1.5 mL/min Column: Phenomenex Luna (2) C18 4.6×150 mm, 5 um)white solid was isolated (25 mg, 25%)

LC-MS m/z 449.5 (M+1) retention time 1.82 ¹H NMR (400 MHz, METHANOL-d₄)d ppm 1.68-1.75 (m, 3 H) 2.38 (ddd, J=13.42, 11.07, 5.17 Hz, 2 H) 2.59(ddd, J=13.46, 10.83, 5.17 Hz, 2 H) 3.09-3.13 (m, 3 H) 3.94 (ddd,J=12.83, 11.07, 5.17 Hz, 1 H) 4.31 (ddd, J=12.93, 10.88, 5.27 Hz, 1 H)6.64 (dt, J=7.07, 1.93 Hz, 1 H) 6.73 (s, 1 H) 6.93-6.99 (m, 1 H)7.05-7.09 (m, 1 H) 7.09-7.13 (m, 1 H) 7.59-7.64 (m, 1 H) 7.71 (d, J=7.02Hz, 1 H)

Example 29N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-2-yloxy)phenyl]pyridin-1(2H)-yl}butanamide

Step A) 2-(4-Bromophenoxy)pyridine

A solution of copper powder (6.4 mg, 0.1 mmol, 0.1 equiv), copper (I)iodide (19 mg, 0.1 mmol, 0.1 equiv), potassium carbonate (484 mg, 3.5mmol, 3.5 equiv), 4-bromophenol (190 mg, 1.1 mmol, 1.1 equiv), and2-bromopyridine (158 mg, 1.0 mmol, 1.0 equiv) in1-methyl-2-pyrrolidinone (1.0 mL) was heated to 140° C. for 5 days. Asolution of 1 M sodium hydroxide (15 mL) was added, and the mixture wasextracted with ethyl acetate (1×30 mL). The organic phase was washedwith 1 M sodium hydroxide (15 mL), dried over anhydrous sodium sulfate,filtered, and concentrated under reduced pressure. The crude materialwas purified by flash chromatography (30% ethyl acetate in heptane) toprovide a colorless oil (190 mg, 76%). MS (LCMS) m/z 250.4 (M+1).

Step B)2-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]pyridine

The title compound (0.23 g, 100%) was prepared from2-(4-bromophenoxy)pyridine (266 mg, 1.1 mmol) andbis(pinacolato)diborane (190 mg, 0.76 mmol) by a general procedureanalogous to that described for the preparation of2-[3-fluoro-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]tetrahydro-2H-pyran,Example 12, step C. MS (LCMS) m/z 298.5 (M+1).

Step C)2-Methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-2-yloxy)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

The title compound (212 mg, 58%) can be prepared from2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]pyridine (239mg, 0.8 mmol) by a procedure analogous to that described for thepreparation of(2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1H-pyrazol-1-yl)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamideExample 1, Step B. MS (LCMS) m/z 540.8 (M−1).

Step D)N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-2-yloxy)phenyl]pyridin-1(2H)-yl}butanamide

Methanol (25 mL) was added to a solution of2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-2-yloxy)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(212 mg, 0.39 mmol) in 4.0 M hydrochloric acid in 1,4-dioxane (4.9 mL)at room temperature. After 1 h, the reaction was concentrated underreduced pressure. The resulting residue was triturated with 10:1 diethylether-methanol, filtered, and dried under reduced pressure to provide awhite solid (168 mg, 88%). LCMS m/z 458.6 (M+1). ¹H NMR (400 MHz, CD₃OD)δ ppm 1.73 (s, 3H), 2.41 (ddd, J=13, 10.5, 5 Hz, 1H), 2.67 (ddd, J=13,10.5, 5 Hz, 1H), 3.11 (s, 3H), 4.06 (ddd, J=13, 11.5 Hz, 1H), 4.39 (ddd,J=13, 11, 5 Hz, 1H), 6.97-7.00 (m, 2H), 7.25 (br d, J=8.7 Hz, 1H), 7.47(d, J=8.8 Hz, 2H), 7.56 (ddd, J=7.4, 5.8, 0.9 Hz, 1H), 7.90-7.94 (m,3H), 8.33 (ddd, J=8.7, 7.4, 1.9 Hz, 1H), 8.47 (ddd, J=5.8, 1.9, 0.6 Hz,1H).

Example 30N-hydroxy-4-{4-[4-(3-hydroxypropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide

Step A)3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]propan-1-ol

To a flask containing 3-(4-iodophenoxy)propan-1-ol (316 mg, 1.14 mmol)(see Qu, W. et. al. Journal of Medicinal Chemistry (2007), 50,3380-3387), bis(pinacolato)diboron (397 mg, 1.56 mmol), potassiumacetate (338 mg, 3.41 mmol), and[1,1′-bis-(diphenylphosphino)ferrocene]-dichloropalladium(II)dichloromethanecomplex (83.4 mg, 0.114 mmol) was added degassed 1,4-dioxane (9.0 mL).The reaction was heated at 80° C. under nitrogen overnight. The reactionwas cooled and diluted with ethyl acetate and water. The organic layerwas separated, dried over magnesium sulfate, filtered, and concentratedin vacuo to give a black solid. Chromatography on silica gel withheptane-ethyl acetate (40% ethyl acetate) gave3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]propan-1-ol asa clear oil (212.5 mg, 67.2%). ¹H NMR (400 MHz, CDCl₃, δ ppm 1.24 (s,12H), 2.02 (m, 2H), 3.84 (m, 2H), 4.06 (t, J=6.05, 2H), 6.66 (d, J=8.59,2H), 7.53 (d, J=8.98, 2H).

Step B)4-(4-(4-(3-hydroxypropoxy)phenyl)-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be prepared as in Preparation 2A (301 mg, 0.622 mmol),3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]propan-1-ol(212 mg, 0.762 mmol), potassium carbonate (434 mg, 3.11 mmol), andtris(dibenzylideneacetone)dipalladium(0) (56.8 mg, 0.062 mmol) werecombined into a flask, placed under vacuum and opened to nitrogen.Degassed dimethoxyethane (2.0 mL) and methanol (2.0 mL) were added andthe reaction was heated at 80° C. under nitrogen for 16 hours. Thereaction was cooled and diluted with ethyl acetate and water. Theaqueous layer was extracted with ethyl acetate and the combined organicswere dried over magnesium sulfate, filtered and evaporated in vacuo ontosilica gel. Chromatography on silica gel with a dichloromethane-methanolgradient (1%-25%) eluted4-(4-(4-(3-hydroxypropoxy)phenyl)-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideas a yellow oil (120 mg, 36.9%). LCMS 521 (M−1).

StepC)N-hydroxy-4-{4-[4-(3-hydroxypropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide

To4-(4-(4-(3-hydroxypropoxy)phenyl)-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(120 mg, 0.230 mmol) was added 4 N hydrogen chloride in dioxane (5.0 mL)and methanol (0.50 mL). The reaction was stirred for 30 minutes and thenevaporated in vacuo onto silica gel. Chromatography on silica gel with adichloromethane-methanol gradient (1%-25%) gave the title compound as awhite foam (20.8 mg, 20.1%). 1H NMR: 400 MHz, (CD₃OD) δ ppm 1.71 (s,3H), 2.06 (m, 2H), 2.38 (ddd, J=13.2, 10.8, 4.8 Hz, 1H), 2.53-2.62 (m,1H), 3.11 (s, 3H), 3.76 (t, J=6.2 Hz, 2H), 3.88-3.96 (m, 1H), 4.14 (t,J=6.3 Hz, 2H), 4.29 (ddd, J=12.5, 10.8, 4.9 Hz, 1H), 6.75 (m, 2H), 7.04(d, J=8.7 Hz, 2H), 7.62-7.69 (m, 3H). LCMS: 437.2 (M−1).

Example 31N-Hydroxy-4-{4-[4-(3-hydroxypropyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide

Step A)4-{4-[4-(3-hydroxypropyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be prepared as in Preparation 2A (320 mg, 0.640 mmol),3-[4-(4,4,5,5-tetramethyl-11,3,2-dioxaborolan-2-yl)phenyl]propan-1-ol(202 mg, 0.770 mmol) (See Takashima, H. et. al. WO 2008105515),potassium carbonate (448 mg, 3.20 mmol), andtris(dibenzylideneacetone)dipalladium(0) (56.8 mg, 0.064 mmol) werecombined into a flask, placed under vacuum and opened to nitrogen.Degassed dimethoxyethane (2.0 mL) and methanol (2.0 mL) were added andthe reaction was heated at 80° C. under nitrogen for 16 hours. Thereaction was cooled and then diluted with ethyl acetate and water. Theaqueous layer was extracted with ethyl acetate and the combined organicswere dried over magnesium sulfate, filtered and evaporated in vacuo ontosilica gel. Chromatography on silica gel with a dichloromethane-methanolgradient (1%-25%) gave4-{4-[4-(3-hydroxypropyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideas a white foam (213.3 mg, 65.6%). LCMS 507.5 (M+1).

Step B)N-hydroxy-4-{4-[4-(3-hydroxypropyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide

To4-{4-[4-(3-hydroxypropyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(213 mg, 0.420 mmol) was added 4 N hydrogen chloride in dioxane (5.0 mL)and methanol (0.50 mL). The reaction was stirred for 30 minutes and thenevaporated to dryness. The residue was dissolved in minimaldichloromethane (2.0 mL) and diluted with ether to produce aprecipitate. The suspension was stirred overnight at room temperature.The resulting solid was allowed to settle and the liquid was decantedoff. The solid was rinsed twice with ether and dried on a vacuum pump togive the title compound as a white solid (164 mg, 92.4%). ¹H NMR (400MHz, CD₃OD, δ ppm 1.72 (s, 3H), 1.83-1.91 (m, 2H), 2.41 (ddd, J=13.4,10.9, 5.4 Hz, 1H), 2.66 (ddd, J=13.6, 10.8, 5.4 Hz, 1H), 2.76 (m, 2H),3.10 (s, 3H), 3.59 (t, J=6.4 Hz, 2H), 4.05 (ddd, J=12.5, 10.5, 5.2 Hz,1H), 4.38 (ddd, J=12.9, 10.7, 5.0 Hz, 1H), 6.95 (d, J=1.8 Hz, 1H), 7.00(m, 1H), 7.38 (br d, J=8.3 Hz, 2H), 7.66 (br d, J=8.3 Hz, 2H), 7.87 (d,J=7.1 Hz, 1H). LCMS: 423.3 (M+1).

Example 32(2R)-N-hydroxy-4-[4-{4-[2-(3-hydroxycyclobutyl)ethoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

Step A) 3-(2-{[Tert-butyl(diphenyl)silyl]oxy}ethyl)cyclobutanol

3-(2-{[Tert-butyl(diphenyl)silyl]oxy}ethyl)cyclobutanone (5.11 g, 14.5mmol) (WO 2006063281) was dissolved in tetrahydrofuran (120 mL). Sodiumborohydride (548 mg, 14.5 mmol) was added and the reaction was stirredovernight at room temperature. The reaction was quenched with water andsaturated aqueous sodium bicarbonate and stirred for 20 min until thebubbling ceased. The reaction mixture was diluted with ether and theaqueous layer was extracted with ether. The combined organic layers werewashed with brine, dried over magnesium sulfate, filtered and evaporatedin vacuo to give 3-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)cyclobutanol(3.58 g, 69.6%) as a clear oil. Partial ¹H NMR indicated a ˜3.5:1 mix ofcis-trans isomers. (CDCl₃, δ ppm, key peaks are 4.08 (quintet, J=7.42,0.78H) and 4.34 (quintet, J=6.83, 0.22H).

Step B)Tert-butyl(diphenyl){2-[3-(tetrahydro-2H-pyran-2-yloxy)cyclobutyl]ethoxy}silane

3-(2-{[Tert-butyl(diphenyl)silyl]oxy}ethyl)cyclobutanol (3.58 g, 10.1mmol) was dissolved in dry tetrahydrofuran (50 mL) and2,3-dihydro-4H-pyran and 4-toluenesulfonic acid pyridine salt were addedand the reaction was stirred at room temperature for 48 hours. Thereaction was concentrated in vacuo and purified on silica gel with aheptane-ethyl acetate gradient (5% ethyl acetate, then 20% ethylacetate) to give crudetert-butyl(diphenyl){2-[3-(tetrahydro-2H-pyran-2-yloxy)cyclobutyl]ethoxy}silane(4.66 g, 105%) as a milky oil. Partial ¹H NMR indicated a ˜4:1 mix ofunknown cis-trans isomers. (CDCl₃, δ ppm, key peaks are 4.05 (m, 0.80H),4.30 (m, 0.20H), 4.52 (m, 0.20H), 4.56 (m, 0.80H).

Step C) 2-[3-(Tetrahydro-2H-pyran-2-yloxy)cyclobutyl]ethanol

Tert-butyl(diphenyl){2-[3-(tetrahydro-2H-pyran-2-yloxy)cyclobutyl]ethoxy}silane(4.66 g, 10.6 mmol) was dissolved in tetrahydrofuran (50 mL) andtetrabutylammonium fluoride (1.0 N in tetrahydrofuran, 1.66 mL, 10.6mmol). The reaction was stirred at room temperature overnight. Thereaction was evaporated in vacuo and purified on silica gel with aheptane-ethyl acetate gradient (10% ethyl acetate, then 50% ethylacetate) to give 2-[3-(tetrahydro-2H-pyran-2-yloxy)cyclobutyl]ethanol(2.14 g, 100%) as a yellow oil. Partial ¹H NMR indicated a ˜4:1 mix ofunknown cis-trans isomers. (CDCl₃, δ ppm, key peaks are 4.07 (m, 0.80H),4.35 (m, 0.20H), 4.54 (m, 0.20H), 4.56 (m, 0.80H).

Step D)2-({3-[2-(4-Bromophenoxy)ethyl]cyclobutyl}oxy)tetrahydro-2H-pyran

2-[3-(Tetrahydro-2H-pyran-2-yloxy)cyclobutyl]ethanol (1.08 g, 5.39 mmol)was dissolved in tetrahydrofuran (20 mL) and was cooled in an ice bath.Triphenylphosphine (2.12 g, 8.09 mmol) and 4-bromo-phenol (1.12 g, 6.47mmol) were added and the reaction was stirred until dissolved.Diethylazodicarboxylate (1.45 g, 8.09 mmol) was added dropwise to thereaction and the reaction was then warmed to room temperature andstirred for 48 hours. The reaction was diluted with ethyl acetate andwashed with 1 N aqueous sodium hydroxide. The organic layer was driedover magnesium sulfate, filtered and evaporated in vacuo to give a clearoil. Purification on silica gel with heptane-ethyl acetate (15% ethylacetate) gave2-({3-[2-(4-bromophenoxy)ethyl]cyclobutyl}oxy)tetrahydro-2H-pyran (622mg, 32.4%) as a clear oil. Partial ¹H NMR indicated a −4:1 mix ofunknown cis-trans isomers. (CDCl₃, δ ppm, key peaks are 4.08 (m, 0.80H),4.38 (m, 0.20H), 6.74 (d, J=8.98, 2H), 7.34 (d, J=9.18, 2H).

Step E)2-[(3-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethyl}cyclobutyl)oxy]tetrahydro-2H-pyran

To a flask containing2-({3-[2-(4-bromophenoxy)ethyl]cyclobutyl}oxy)tetrahydro-2H-pyran (622mg, 1.75 mmol), bis(pinacolato)diboron (612 mg, 2.41 mmol), potassiumacetate (521 mg, 5.25 mmol), and[1,1′-bis-(diphenylphosphino)ferrocene]-dichloropalladium(II)dichloromethanecomplex (128 mg, 0.175 mmol) was added deoxygenated 1,4-dioxane (8.0mL). The reaction was heated at 80° C. under nitrogen overnight. Thereaction was cooled, diluted with ether and filtered through a pad ofcelite. The filtrate was evaporated in vacuo to give a black oil.Chromatography on silica gel with heptane-ethyl acetate (33% ethylacetate) gave2-[(3-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethyl}cyclobutyl)oxy]tetrahydro-2H-pyranas a clear oil (845 mg, 120%). Partial ¹H NMR indicated a ˜3.5:1 mix ofunknown cis-trans isomers. (CDCl₃, δ ppm, key peaks are 1.31 (s, 12H),4.08 (m, 0.78H), 4.38 (m, 0.22H), 6.85 (d, J=8.59, 2H), 7.72 (d, J=8.79,2H).

Step F)(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-{2-[3-(tetrahydro-2H-pyran-2-yloxy)cyclobutyl]ethoxy}phenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2 B (334 mg, 0.670 mmol),2-[(3-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethyl}cyclobutyl)oxy]tetrahydro-2H-pyran(324 mg, 0.804 mmol), potassium carbonate (463 mg, 3.35 mmol), andpalladium II EnCat (172 mg, 0.067 mmol) were combined into a flask,placed under vacuum and opened to nitrogen. Deoxygenated 1,4-dioxane(2.0 mL) and water (0.50 mL) were added and the reaction was heated at80° C. under nitrogen overnight. The reaction was cooled, diluted withethyl acetate and filtered through celite. The celite was washed withethyl acetate and the filtrate was evaporated in vacuo onto silica gel.Chromatography on silica gel with a dichloromethane-methanol gradient(1%-25%) gave(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-{2-[3-(tetrahydro-2H-pyran-2-yloxy)cyclobutyl]ethoxy}phenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamideas a tan foam (386 mg, 89.1%). LCMS 645.8 (M−1).

Step G)(2R)-N-hydroxy-4-[4-{4-[2-(3-hydroxycyclobutyl)ethoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

To(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-{2-[3-(tetrahydro-2H-pyran-2-yloxy)cyclobutyl]ethoxy}phenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(386 mg, 0.597 mmol) was added 4 N hydrogen chloride in dioxane (6.0 mL)and methanol (0.60 mL). The reaction was stirred for 30 minutes and thenevaporated in vacuo to give a yellow oil. The residue was dissolved in aminimal amount of methanol (0.50 mL) and diluted with ether to give ayellow precipitate. This suspension was stirred overnight at roomtemperature. The solid was allowed to settle and the liquid was decantedoff. The solid was rinsed twice with ether and dried on a vacuum pump togive the title compound as a white solid (229 mg, 80.5%). ¹H NMR (poorresolution in spectra) (400 MHz, METHANOL-d₄) δ ppm 1.55-1.63 (m, 2 H)1.69-1.73 (m, 3 H) 1.87-1.97 (m, 3 H) 2.11 (t, J=6.83 Hz, 0 H) 2.36-2.50(m, 3 H) 2.61-2.72 (m, 1 H) 3.08-3.11 (m, 3 H) 3.99-4.10 (m, 4 H)4.32-4.42 (m, 1 H) 6.89-6.97 (m, 1 H) 7.00-7.07 (m, 3 H) 7.67-7.73 (m, 2H) 7.87 (t, J=10.54 Hz, 1 H). LCMS 479.6 (M+1).

Example 33(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A)(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Pd EnCat™ (130 mg, 0.051 mmol) was added to a mixture of potassiumcarbonate (221 mg, 1.60 mmol), 1-benzofuran-2-ylboronic acid (271 mg,0.954 mmol), and4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2A (240 mg, 0.63 mmol) indioxane:water (5 mL, 4:1) in a 2-5 mL microwave vial and the reactionwas heated at 90° C. overnight. The reaction was filtered and the resinwas washed with ethyl acetate (50 mL) and water (50 mL). The filtratewas concentrated to dryness and the crude was purified via flashchromatography on an Analogix SF15-12g column and eluted with ethylacetate in heptane (0-80%) to afford the title compound as a white solid(105 mg, 42.8%). LC-MS m/z 487.7 (M−1).

Step B)(+/−)-4-[4-(1-Benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

A 4.0 M solution of HCl in 1,4-dioxane (5 mL) was added slowly to asolution of(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(105 mg, 0.22 mmol) in dichloromethane (5 mL) with water (1.0 mL) at 0°C. The ice bath was removed and the reaction was allowed to warm to rt.After 30 min (complete by TLC), the reaction was concentrated to afforda crude white solid. The crude was triturated in isopropanol (5 mL)overnight. The solid was collected via filtration, washed withisopropanol (5 mL), isopropanol:heptane (1:1, 5 mL), heptane (5 mL), andether (5 mL). The solid was collected by filteration and dried undervacuum to afford a white solid (86.1 mg, 99%). LC-MS m/z 405.5 (M+1). ¹HNMR (400 MHz, DMSO-d₆) δ ppm 1.57 (s, 3 H) 2.10-2.23 (m, 1 H) 2.39-2.48(m, 1 H) 3.11 (s, 3 H) 3.71-3.81 (m, 1 H) 4.05-4.15 (m, 1 H) 6.78-6.89(m, 2 H) 7.27-7.35 (m, 1 H) 7.37-7.45 (m, 1 H) 7.63-7.82 (m, 4 H).

Example 34(+/−)-N-hydroxy-4-[4-(6-methoxy-2-naphthyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

Step A)(+/−)-4-[4-(6-methoxy-2-naphthyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(+/−)-4-(4-Iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2A and(6-methoxy-2-naphthyl)boronic acid were converted to the title productfollowing the general procedure outlined for(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(Example 33, Step A). The title compound was obtained as a white solid(452.7 mg, 85.3%) LC-MS m/z 529.7 (M+1).

Step B)N-hydroxy-4-[4-(6-methoxy-2-naphthyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

(+/−)-4-[4-(6-Methoxy-2-naphthyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewas converted to the title product following the general procedureoutlined for(+/−)-4-[4-(1-Benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

(Example 33, Step B). The title compound was obtained as a white solid(101.2 mg, 69.9%) LC-MS m/z 445.3 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δ ppm1.59 (s, 3 H) 2.13-2.27 (m, 1 H) 2.37-2.49 (m, 1 H) 3.12 (s, 3 H)3.70-3.84 (m, 1 H) 3.90 (s, 3 H) 4.06-4.25 (m, 1 H) 6.77-6.89 (m, 2 H)7.18-7.26 (m, 1 H) 7.38 (d, J=2.54 Hz, 1 H) 7.76-7.86 (m, 2 H) 7.87-7.97(m, 2 H) 8.29 (d, J=1.76 Hz, 1 H) 11.18 (br. s., 1 H).

Example 35N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyridin-4-ylphenyl)pyridin-1(2H)-yl]butanamide

Step A)(+/−)-2-Methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyridin-4-ylphenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(+/−)-4-(4-Iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be prepared as in Preparation 2A and4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyridine wereconverted to the title product following the general procedure outlinedfor(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidein Example 33, Step A. The title compound was obtained as a white solid(161 mg, 61%) LC-MS m/z 526.7 (M+1).

Step B)(+/−)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyridin-4-ylphenyl)pyridin-1(2H)-yl]butanamide

(+/−)-2-Methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyridin-4-ylphenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewas converted to the title product following the general procedureoutlined for(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamidein Example 33, Step B. The title compound was obtained as a white solid(90 mg, 62%) LC-MS m/z 442.3 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.58(s, 3 H) 2.09-2.24 (m, 1 H) 2.44 (m, 1 H) 3.11 (s, 3 H) 3.72-3.82 (m, 1H) 4.07-4.22 (m, 1 H) 6.69-6.78 (m, 1 H) 6.84 (d, J=1.95 Hz, 1 H) 7.82(d, J=7.03 Hz, 1 H) 7.98 (d, J=8.59 Hz, 2 H) 8.12 (d, J=8.59 Hz, 2 H)8.36 (d, J=5.86 Hz, 2 H) 8.93 (d, J=6.25 Hz, 2 H) 11.15 (br. s., 1 H)

Example 36N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-quinolin-7-ylpyridin-1(2H)-yl)butanamide

Step A) Quinolin-7-yl trifluoromethanesulfonate

Trifluoromethanesulfonic anhydride (1.40 mL, 8.32 mmol) was addeddropwise via a syringe to a solution of quinolin-7-ol (930 mg, 6.41mmol), and pyridine (1.05 mL, 13.0 mmol) in anhydrous dichloromethane(50 mL) at 0° C. After addition the ice bath was removed and thereaction was allowed to warm to room temperature and stirred overnight.The reaction was concentrated and purified via flash chromatographyusing an Analogix SF25-40g column and eluant of ethyl acetate in heptane(0-40%) to afford the title compound as an orange-white solid (1.54 g,86.7%). LC-MS m/z 278.4 (M+1). ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm7.42-7.57 (m, 2H) 7.95 (d, J=8.98 Hz, 1H) 8.05 (d, J=2.54 Hz, 1H)8.20-8.29 (m, 1H) 8.97-9.06 (m, 1H).

Step B) 7-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)auinoline

Potassium acetate (391 mg, 3.98 mmol) was added to a solution ofquinolin-7-yl trifluoromethanesulfonate (370 mg, 1.32 mmol),4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (405 mg, 1.60mmol), and [1,1′-bis-(diphenylphosphino)ferrocene]-dichloropalladium(II)dcm complex (325 mg, 0.40 mmol) in 1,4-dioxane (5.0 mL) in a 20 mL vial.The vial was capped and heated to 80° C. and stirred at this temperatureovernight. The reaction was allowed to cool, diluted with ethyl acetate(25 mL) and water (25 mL), filtered through celite (˜1 inch) and thefilter pad was washed with ethyl acetate (10 mL). The organic layer wasseparated, and the aqueous layer was extracted with ethyl acetate (2×30mL). The combined organics were dried (MgSO₄), filtered, andconcentrated. Crude material was purified via flash chromatography usingan Analogix SF15-24g column and ethyl acetate in heptane (0-50%) as theeluant to afford the title compound as a white solid (277 mg, 81.3%).LC-MS m/z 256.5 (M+1). ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 12H) 7.40-7.45 (m, 1 H) 7.81 (d, J=8.01 Hz, 1 H) 7.88-7.95 (m, 1 H)8.12-8.18 (m, 1 H) 8.62 (d, J=0.78 Hz, 1 H) 8.83-9.01 (m, 1 H)

Step C)(+/−)-2-Methyl-2-(methylsulfonyl)-4-(2-oxo-4-quinolin-7-lpyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(+/−)-4-(4-Iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2A and7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline were convertedto the title product following the general procedure outlined for(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidein Example 33, Step A. The title compound was obtained as a white solid(221 mg, 88.1%) LC-MS m/z 500.7 (M+1).

Step D)N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-quinolin-7-ylpyridin-1(2H)-yl)butanamide,hydrochloride salt

2-Methyl-2-(methylsulfonyl)-4-(2-oxo-4-quinolin-7-ylpyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewas converted to the title product following the general procedureoutlined for(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamidein Example 33, Step B. Purification was performed using prepratory HPLCto afford the title compound as a white solid (65.5 mg, 32.8%) LC-MS m/z416.6 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δ ppm ¹H NMR (400 MHz, DMSO-d₆) δppm 1.60 (s, 3 H) 2.14-2.26 (m, 1 H) 2.41-2.48 (m, 1 H) 3.12 (s, 3 H)3.72-3.86 (m, 1 H) 4.09-4.22 (m, 1 H) 6.84-6.88 (m, 1 H) 6.90 (d, J=2.15Hz, 1 H) 7.56-7.65 (m, 1 H) 7.83 (d, J=7.23 Hz, 1 H) 7.93-8.02 (m, 1 H)8.10 (d, J=8.40 Hz, 1 H) 8.35 (d, J=1.76 Hz, 1 H) 8.40-8.47 (m, 1 H)8.94-9.02 (m, 1 H) 9.27 (d, J=1.56 Hz, 1 H) 11.17 (s, 1 H).

Example 37N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2-pyridin-4-ylethoxy)phenyl]pyridin-1(2H)-yl}butanamide

Step A) 4-[2-(4-Bromophenoxy)ethyl]pyridine

Diethyl azodicarboxylate (4.44 mL, mmol, 40%) was slowly added to asolution of 2-pyridin-4-yl-ethanol (1.00 g, 8.12 mmol),triphenylphosphine (2.56 g, 9.74 mmol), and 4-bromophenol (1.40 g, 8.12mmol) in THF (40.6 mL) at 0° C. under nitrogen. The reaction was allowedto warm to room temperature and stirred overnight. The reaction mixturewas quenched with water (150 mL) and extracted with ethyl acetate (200mL). The organics were washed with 1N aqueous NaOH (100 mL) and brine(100 mL). The organics were dried (Na₂SO₄), filtered, and concentrated.The crude material was crystallized with ether:heptanes (1:1, ˜25 mL)and the solid was removed via filtration and washed with ether:heptanes.The combined filtrates were concentrated and further purified via flashchromatography using an Analogix SF25-40g column and ethyl acetate inheptane (0-30%) as the eluant to afford the title compound as a clearliquid (1.20 g, 46.2%). LC-MS m/z 278.4 (M+1). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 3.11 (t, 2 H) 4.19 (t, J=6.44 Hz, 2 H) 6.77 (d,J=8.98 Hz, 2 H) 7.22-7.26 (m, 2 H) 7.38 (d, J=4.69 Hz, 2 H) 8.54-8.57(m, 3 H)

Step B)4-{2-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethyl}pyridine

Potassium acetate (391 mg, 3.98 mmol) was added to a solution of4-[2-(4-bromophenoxy)ethyl]pyridine (370 mg, 1.33 mmol),4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (405 mg, 1.60mmol), and [1,1′-bis-(diphenylphosphino)ferrocene]-dichloropalladium(II)dcm complex (325 mg, 0.40 mmol) in 1,4-dioxane (5.0 mL) in a 20 mL vial.The vial was capped and heated to 80° C. and stirred at this temperatureovernight. [1,1′-bis-(diphenylphosphino)ferrocene]-dichloropalladium(II)dcm complex (325 mg, 0.40 mmol) was added to the reaction and themixture was reheated to 80° C. and stirring was continued at thistemperature overnight. The reaction was cooled, diluted with ethylacetate (25 mL) and water (25 mL), filtered through celite (−1 inch) andthe filter pad was washed with ethyl acetate (10 mL). The organic layerwas separated, and the aqueous layer was extracted with ethyl acetate(2×30 mL). The combined organics were dried (MgSO₄), filtered, andconcentrated. The crude was purified via flash chromatography using anAnalogix SF15-24g column and ethyl acetate in heptane (30-80%) as theeluant to afford the title compound as an orange-solid (547 mg, 85.3%).LC-MS m/z 326.6 (M+1).

Step C)(+/−)-2-Methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2-pyridin-4-ylethoxy)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(+/−)-4-(4-Iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewhich may be produced as in Preparation 2A and4-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethyl}pyridinewere converted to the title product following the general procedureoutlined for(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidein Example 33, Step A. The title compound was obtained as a white solid(44.1 mg, 15.4%) LC-MS m/z 568.8 (M−1).

Step D)N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2-pyridin-4-ylethoxy)phenyl]pyridin-1(2H)-yl}butanamide,hydrochloride salt

(+/−)-2-Methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2-pyridin-4-ylethoxy)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewas converted to the title compound following the general procedureoutlined for(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamidein Example 33, Step B. The title compound was obtained as a white solid(11.2 mg, 30%) LC-MS m/z 486.6 (M+1). ¹H NMR (400 MHz, METHANOL-d₄) δppm 1.70 (s, 3 H) 2.28-2.46 (m, 1 H) 2.49-2.69 (m, 1 H) 3.11 (s, 3 H)3.48 (t, J=5.47 Hz, 2 H) 3.93 (dt, 1 H) 4.20-4.37 (m, 1 H) 4.47 (t,J=5.76 Hz, 2 H) 6.75 (br. s., 1 H) 7.04 (d, J=8.20 Hz, 1 H) 7.67 (m,J=8.20 Hz, 3 H) 8.12 (d, J=5.86 Hz, 2 H) 8.78 (d, J=5.66 Hz, 2 H).

Example 38(2R)-N-hydroxy-2-methyl-4-{4-[4-(5-methyl-1,3-oxazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide

Step A)5-Methyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3-oxazole

2-(4-Bromophenyl)-5-methyl-1,3-oxazole was converted to the titleproduct following the general procedure outlined for4-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethyl}pyridinein Example 37, Step B. The title compound was obtained as an orangesolid (221.5 mg, 71.7%) LC-MS m/z 286.4 (M+1). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.37 (s, 12 H) 2.41 (d, J=1.17 Hz, 3 H) 6.81-6.92(m, 1 H) 7.88 (d, J=8.39 Hz, 2 H) 8.00 (d, J=8.39 Hz, 2 H).

Step B)(2R)-2-methyl-4-{4-[4-(5-methyl-1,3-oxazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-(4-Iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2B, and5-Methyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3-oxazolewere converted to the title compound following the general procedureoutlined for(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidin Example 33, step A. The title compound was obtained as a white solid(121 mg, 61%) LC-MS m/z 514.7 (M−1).

Step C)(2R)-N-hydroxy-2-methyl-4-{4-[4-(5-methyl-1,3-oxazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide

(2R)-2-methyl-4-{4-[4-(5-methyl-1,3-oxazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewas converted to the title compound following the general procedureoutlined for(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide,in Example 33, Step B The title compound was obtained as an off-whitesolid (56 mg, 68%). LC-MS m/z 446.5 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δppm 1.58 (s, 3 H) 2.07-2.23 (m, 1 H) 2.36-2.48 (m, 4 H) 3.11 (s, 3 H)3.65-3.86 (m, 1 H) 4.03-4.19 (m, 1 H) 6.67-6.74 (m, 1 H) 6.78 (d, J=1.95Hz, 1 H) 7.04 (d, J=1.17 Hz, 1 H) 7.80 (d, J=7.23 Hz, 1 H) 7.89 (d,J=8.59 Hz, 2 H) 8.01 (d, J=8.59 Hz, 2 H) 11.15 (br. s., 1 H)

Example 39(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyrimidin-2-ylphenyl)pyridin-1(2H)-yl]butanamide

Step A)2-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidine

2-(4-Bromophenyl)pyrimidine was converted to the title product followingthe general procedure outlined for4-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethyl}pyridinein Example 37, Step B. The title compound was obtained as an orangesolid (242.8 mg, 59.3%) LC-MS m/z 283.4 (M+1). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.38 (s, 12 H) 7.21 (t, J=4.88 Hz, 1 H) 7.27 (s, 1H) 7.95 (d, J=8.39 Hz, 2 H) 8.45 (d, J=8.59 Hz, 2 H) 8.84 (d, J=4.88 Hz,2 H)

Step B)(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyrimidin-2-ylphenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewhich may be produced as in Preparation 2B and2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidine wereconverted to the title compound following the general procedure outlinedfor(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidein Example 33, Step A. The title compound was obtained as a yellow solid(166 mg, 78.6%) LC-MS m/z 525.7 (M−1).

Step C)(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyrimidin-2-ylphenyl)ppyridin-1(2H)-yl]butanamide

(2R)-2-Methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyrimidin-2-ylphenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewas converted to the title compound following the general procedureoutlined for(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamidein Example 33, Step B. The title compound was obtained as an off-whitesolid (76 mg, 55%). LC-MS m/z 443.5 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δppm 1.59 (s, 3 H) 2.14-2.25 (m, 1 H) 2.38-2.48 (m, 1 H) 3.09 (s, 3 H)3.71-3.83 (m, 1 H) 4.04-4.20 (m, 1 H) 6.68-6.78 (m, 1 H) 6.80 (d, J=2.15Hz, 1 H) 7.49 (t, J=4.88 Hz, 1 H) 7.80 (d, J=7.02 Hz, 1 H) 7.90 (d,J=8.59 Hz, 2 H) 8.49 (d, J=8.59 Hz, 2 H) 8.95 (d, J=4.88 Hz, 2 H) 11.16(s, 1 H).

Example 40(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}butanamide

Step A)2-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2H-1,2,3-triazole

2-(4-Bromophenyl)-2H-1,2,3-triazole was converted to the title productfollowing the general procedure outlined for4-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethyl}pyridinein Example 37, Step B. The title compound was obtained as an orangesolid (240.6 mg, 78%) LC-MS m/z 272.4 (M+1). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.37 (s, 12 H) 7.83 (s, 2 H) 7.94 (d, J=8.59 Hz, 2H) 8.10 (d, J=8.59 Hz, 2 H).

Step B)(2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2A, and2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2H-1,2,3-triazolewere converted to the title compound following the general procedureoutlined for(+/−)-4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidein Example 33, Step A. The title compound was obtained as a white solid(101 mg, 48.8%) LC-MS m/z 514.7 (M−1).

Step C)(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}butanamide

(2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewas converted to the title compound following the general procedureoutlined for(+/−)-4-[4-(1-Benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamidein Example 33, Step B. The title compound was obtained as an off-whitesolid (63.7 mg, 74%). LC-MS m/z 432.5 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δppm 1.58 (s, 3 H) 2.09-2.25 (m, 1 H) 2.34-2.47 (m, 1 H) 3.11 (s, 3 H)3.70-3.82 (m, 1 H) 4.04-4.19 (m, 1 H) 6.68-6.73 (m, 1 H) 6.78 (d, J=2.15Hz, 1 H) 7.79 (d, J=7.22 Hz, 1 H) 7.95 (d, J=8.78 Hz, 2 H) 8.12 (d,J=8.59 Hz, 2 H) 8.17 (s, 2 H) 11.15 (br. s., 1 H).

Example 412R)-4-[4-(4-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)-butanamide

Step A)(2R)-4-[4-(4-fluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Pd EnCat™ (200 mg, 0.06 mmol) was added to a mixture of potassiumcarbonate (250 mg, 1.81 mmol), (4-fluorophenyl)boronic acid (84 mg,0.602 mmol), and(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2 B, (300 mg, 0.602 mmol) indioxane:water (5.5 mL, 10:1mixture) in a 25 mL round bottom flask. Theflask was heated overnight at 80° C. The reaction was cooled to ambienttemperature and filtered through celite and washed with ethyl acetate(20 mL). The crude material was concentrated, and purified bychromatography on silica gel (gradient: 100:0 dichloromethane:methanolto 95:5 dichloromethane:methanol) to provide title compound as aviscous, foamy oil. Yield: 257 mg, 91.5%. MS (APCI) m/z 467.6 (M+H) 1HNMR (400 MHz, CHLOROFORM-d) δ ppm 1.54-1.65 (m, 3H) 1.68 (d, J=2.34 Hz,3 H) 1.71-1.99 (m, 3 H) 2.32-2.44 (m, 1 H) 2.44-2.57 (m, 1 H) 3.18 (d,J=2.93 Hz, 3 H) 3.54-3.66 (m, 1 H) 3.97-4.10 (m, 1 H) 4.11-4.25 (m, 1 H)4.25-4.38 (m, 1 H) 5.16 (d, J=15.81 Hz, 1 H) 6.48 (dd, J=6.93, 1.27 Hz,1 H) 6.76 (s, 1 H) 7.12 (t, J=8.59 Hz, 2 H) 7.39 (d, J=7.02 Hz, 1 H)7.47-7.57 (m, 2 H) 12.15 (d, J=7.42 Hz, 1 H)

Step B)(2R)-4-[4-(4-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

A solution of 1.0 M aqueous HCl (2.76 mL) was added slowly to a solutionof(2R)-4-[4-(4-fluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(257 mg, 0.55 mmol) in 2-propanol (15 mL) at room temperature. Thereaction was allowed to stir at room temperature overnight. After 18hours the reaction was concentrated to afford a brown solid. Crudematerial was triturated in ethyl acetate (50 mL) for 1 hour; the solidwas collected via filtration and washed with hexanes (20 mL). The solidwas allowed to dry on the filter under high vacuum to afford anoff-white solid. Yield 153 mg, 73%. MS (APCI) m/z 383.6 (M+H), 1H NMR(400 MHz, DMSO-d₆) δ ppm 1.55 (s, 3 H) 2.08-2.19 (m, 1 H) 2.34-2.44 (m,1 H) 3.08 (s, 3 H) 3.64-3.80 (m, 1 H) 4.04-4.13 (m, 1 H) 6.62 (dd,J=7.02, 2.15 Hz, 1 H) 6.67 (d, J=1.95 Hz, 1 H) 7.20-7.41 (m, 2 H)7.64-7.84 (m, 3 H) 11.12 (br. s., 1 H)

Example 42(2R)-4-[4-(3-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A)(2R)-4-[4-(3-fluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

The title compound was produced following the general method of Example41, Step A, using (3-fluorophenyl)boronic acid (84 mg, 0.602 mmol). Thecrude product was purified by chromatography on silica gel (elutionsolvent: ethyl acetate) to provide title compound as a viscous, foamyoil. Yield: 125 mg, 44.5%. MS (APCI) m/z 489.6 (M+Na) 1H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.54-1.65 (m, 3 H) 1.67-1.71 (m, 3 H) 1.71-1.97 (m,3 H) 2.32-2.44 (m, 1 H) 2.45-2.58 (m, 1 H) 3.19 (d, J=3.32 Hz, 3 H)3.53-3.70 (m, 1 H) 3.98-4.07 (m, 1 H) 4.12-4.25 (m, 1 H) 4.27-4.40 (m, 1H) 5.11-5.21 (m, 1 H) 6.49 (dd, J=6.83, 1.76 Hz, 1 H) 6.79 (s, 1 H)7.08-7.16 (m, 1 H) 7.20-7.28 (m, 1 H) 7.29-7.36 (m, 1 H) 7.37-7.44 (m, 2H) 12.10 (d, J=6.05 Hz, 1 H)

Step B)(2R)-4-[4-(3-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Title compound was produced using the general methodology of Example 41,Step B affording an off-white solid. Yield 55 mg, 54%. MS (APCI) m/z383.5 (M+H).¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.55 (s, 3 H) 2.14 (td,J=12.05, 5.17 Hz, 1 H) 2.40 (td, J=12.24, 4.78 Hz, 1 H) 3.08 (s, 3 H)3.73 (td, J=11.95, 4.78 Hz, 1 H) 4.02-4.14 (m, 1 H) 4.17-4.42 (m, 1 H)6.65 (dd, J=7.12, 2.05 Hz, 1 H) 6.74 (d, J=1.95 Hz, 1 H) 7.21-7.33 (m, 1H) 7.43-7.63 (m, 3 H) 7.75 (d, J=7.22 Hz, 1 H) 11.11 (br. s., 1 H)

Example 43(2R)-4-[4-(2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A)(2R)-4-[4-(2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Title compound was produced by following the general method of Example41, Step A, using (2-fluorophenyl)boronic acid (84 mg, 0.602 mmol). Thecrude material was purified by chromatography on silica gel (elutionsolvent: ethyl acetate) to provide title compound as a viscous, foamyoil. Yield: 180 mg, 64.1%. MS (APCI) m/z 489.6 (M+Na) 1H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.49-1.66 (m, 3 H) 1.69 (d, J=2.34 Hz, 3 H)1.71-1.97 (m, 3 H) 2.28-2.45 (m, 1 H) 2.45-2.59 (m, 1 H) 3.19 (d, J=2.93Hz, 3 H) 3.54-3.70 (m, 1 H) 3.92-4.07 (m, 1 H) 4.12-4.24 (m, 1 H)4.28-4.39 (m, 1 H) 5.10-5.21 (m, 1 H) 6.50 (d, J=7.02 Hz, 1 H) 6.79 (s,1 H) 7.10-7.17 (m, 1 H) 7.18-7.24 (m, 1 H) 7.34-7.43 (m, 3 H) 12.15 (d,J=7.42 Hz, 1 H)

Step B)(2R)-4-[4-(2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Title compound was produced using the general methodology of Example 41,Step B affording an off-white solid. Yield 71 mg, 48%. MS (APCI) m/z383.5 (M+H). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.55 (s, 3 H) 2.05-2.21 (m,1 H) 2.35-2.45 (m, 1 H) 3.08 (s, 3 H) 3.73 (td, J=12.15, 4.59 Hz, 1 H)4.10 (td, J=11.90, 5.07 Hz, 1 H) 4.16-4.34 (m, 1 H) 6.46 (dt, J=6.98,1.88 Hz, 1 H) 6.55 (s, 1 H) 7.23-7.36 (m, 2 H) 7.42-7.52 (m, 1 H) 7.56(td, J=7.90, 1.56 Hz, 1 H) 7.73 (d, J=7.02 Hz, 1 H) 11.10 (br. s., 1 H)

Example 44(2R)-4-[4-(2,3-difluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A)(2R)-4-[4-(2,3-difluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Title compound was produced by following the general method of Example41, Step A, using (2,3-difluoro-4-methoxyphenyl)boronic acid (113 mg,0.602 mmol. The resulting crude material was purified by chromatographyon silica gel (elution solvent: ethyl acetate) to provide title compoundas a viscous, foamy oil. Yield: 132 mg, 42.6%. MS (APCI) m/z 515.5 (M+H)1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.54-1.66 (m, 3 H) 1.68 (d, J=2.34Hz, 3 H) 1.71-1.97 (m, 3 H) 2.30-2.44 (m, 1 H) 2.45-2.58 (m, 1 H) 3.18(d, J=3.12 Hz, 3 H) 3.54-3.68 (m, 1 H) 3.92 (s, 3 H) 3.99-4.08 (m, 1 H)4.11-4.23 (m, 1 H) 4.26-4.40 (m, 1 H) 5.10-5.21 (m, 1 H) 6.42-6.53 (m, 1H) 6.75 (s, 1 H) 6.77-6.86 (m, 1 H) 7.05-7.17 (m, 1 H) 7.37 (d, J=7.02Hz, 1 H) 12.10 (d, J=7.61 Hz, 1 H)

Step B)(2R)-4-[4-(2,3-difluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

A solution of 1.0 M aqueous HCl (2.76 mL) was added slowly to a solutionof(2R)-4-[4-(2,3-difluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(132 mg, 0.26 mmol) in 1,4-dioxane (15 mL) at room temperature. Thereaction was allowed to stir at room temperature overnight. After 18hours the reaction was concentrated to 25% of the original volume,resulting in a white precipitate. The precipitate was filtered viaBuchner funnel and washed with hexanes (20 mL) to afford a white solid.Yield 45 mg, 41%. MS (APCI) m/z 431.1 (M+H). ¹H NMR (400 MHz, DMSO-d₆) δppm 1.55 (s, 3 H) 2.14 (td, J=12.20, 4.88 Hz, 1 H) 2.35-2.45 (m, 1 H)3.08 (s, 3 H) 3.72 (td, J=12.05, 4.78 Hz, 1 H) 3.90 (s, 3 H) 4.09 (td,J=11.90, 5.27 Hz, 1 H) 6.46 (dt, J=7.02, 1.85 Hz, 1 H) 6.54 (s, 1 H)7.03-7.17 (m, 1 H) 7.37 (td, J=8.63, 2.24 Hz, 1 H) 7.72 (d, J=7.22 Hz, 1H) 9.22 (br. s., 1 H) 11.10 (s, 1H)

Example 45(2R)-4-[4-(3-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A)(2R)-4-[4-(3-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Title compound was produced by following the general method of Example41, Step A, using (3-chloro-2-fluorophenyl)boronic acid (105 mg, 0.602mmol). The crude material was purified by chromatography on silica gel(elution solvent: ethyl acetate) to provide title compound as a viscous,foamy oil. Yield: 137 mg, 45.4%. MS (APCI (type)) m/z 523.5 (M+Na). 1HNMR (400 MHz, CHLOROFORM-d) δ ppm 1.55-1.66 (m, 3 H) 1.70 (d, J=2.34 Hz,3 H) 1.73-1.98 (m, 3 H) 2.33-2.45 (m, 1 H) 2.47-2.63 (m, 1 H) 3.20 (d,J=3.71 Hz, 3 H) 3.55-3.72 (m, 1 H) 3.99-4.11 (m, 1 H) 4.12-4.25 (m, 1 H)4.30-4.41 (m, 1 H) 5.11-5.23 (m, 1 H) 6.45-6.51 (m, 1 H) 6.78 (d, J=0.78Hz, 1 H) 7.13-7.20 (m, 1 H) 7.26-7.33 (m, 1 H) 7.40 (d, J=7.02 Hz, 1 H)7.43-7.50 (m, 1 H) 12.04 (d, J=4.29 Hz, 1 H)

Step B)(2R)-4-[4-(3-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Title compound was produced using the general methodology of Example 44,Step B. Yield 64 mg, 56%. MS (APCI) m/z 417.5 (M+H). ¹H NMR (400 MHz,DMSO-d₆) δ ppm 1.55 (s, 3 H) 2.14 (td, J=12.05, 4.98 Hz, 1 H) 2.33-2.45(m, 1 H) 3.08 (s, 3 H) 3.74 (td, J=11.71, 4.68 Hz, 1 H) 4.10 (td,J=11.85, 4.98 Hz, 1 H) 6.47 (d, J=7.22 Hz, 1 H) 6.57 (s, 1 H) 7.31 (t,J=7.81 Hz, 1 H) 7.52 (t, J=6.93 Hz, 1 H) 7.66 (d, J=14.83 Hz, 1 H) 7.75(d, J=6.83 Hz, 1 H) 9.22 (br. s., 1 H) 11.09 (s, 1 H)

Example 46(2R)-4-[4-(2,3-dichlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A)(2R)-4-[4-(2,3-dichlorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Title compound was produced by following the general method of Example41, Step A, using (2,3-dichlorophenyl)boronic acid (115 mg, 0.602 mmol).The resulting crude material was purified by chromatography on silicagel (elution solvent: ethyl acetate) to provide title compound as aviscous, foamy oil. Yield: 142 mg, 45.6%. MS (APCI (type)) m/z 539.5(M+Na). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.53-1.67 (m, 3 H)1.68-1.73 (m, 3 H) 1.73-1.98 (m, 3 H) 2.36-2.48 (m, 1 H) 2.48-2.61 (m, 1H) 3.20 (d, J=4.49 Hz, 3 H) 3.57-3.73 (m, 1 H) 3.96-4.09 (m, 1 H)4.12-4.25 (m, 1 H) 4.27-4.49 (m, 1 H) 5.03-5.32 (m, 1 H) 6.21-6.42 (m, 1H) 6.62 (d, J=1.76 Hz, 1 H) 7.00-7.19 (m, 1 H) 7.21-7.29 (m, 1 H) 7.38(d, J=7.02 Hz, 1 H) 7.51 (dd, J=8.00, 1.56 Hz, 1 H) 12.03 (s, 1 H)

Step B)(2R)-4-[4-(2,3-dichlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Title compound was produced using the general methodology of Example 44,Step B. Yield 30 mg, 25%. MS (APCI) m/z 433.4 (M+H). ¹H NMR (400 MHz,DMSO-d₆) δ ppm 1.55 (s, 3 H) 2.10-2.21 (m, 1 H) 2.31-2.42 (m, 1 H) 3.08(s, 3 H) 3.74 (td, J=12.00, 4.88 Hz, 1 H) 4.10 (td, J=11.85, 4.78 Hz, 1H) 6.34 (dd, J=7.02, 1.95 Hz, 1 H) 6.40 (d, J=1.95 Hz, 1 H) 7.33-7.39(m, 1 H) 7.40-7.48 (m, 1 H) 7.69 (dd, J=7.90, 1.66 Hz, 1 H) 7.73 (d,J=7.02 Hz, 1 H) 9.22 (s, 1 H) 11.09 (s, 1 H)

Example 47(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(tetrahydro-2H-pyran-4-yl)phenyl]pyridin-1(2H)-yl}butanamide

Step A)4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]tetrahydro-2H-pyran

To a solution of 4-(4-bromophenyl)tetrahydro-2H-pyran (250 mg, 1.04mmol) in dioxane (7 mL) was added4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (290 mg, 1.14mmol) and potassium acetate (210 mg, 2.07 mmol), followed by PdCl₂(dppf)(80.1 mg, 0.104 mmol, 10 mol %). The reaction mixture was stirred at 80°C. for overnight. The reaction was cooled to room temperature then added5 mL of water and 10 mL of ethyl acetate. The aqueous layer wasextracted with ethyl acetate (10 mL×3) and the combined organics weredried with sodium sulfate, filtered and concentrated. The residue waspurified by chromatography on silica gel (Gradient: 0% to 100% ethylacetate in heptane) to give the title compound as a solid (33.8%). ¹HNMR (400 MHz, DMSO-d₆) δ ppm 1.29 (s, 1 H) 1.28 (s, 11 H) 1.64 (br. s.,4 H) 2.77 (br. s., 1 h) 3.42 (br. s., 2 H) 3.92 (br. s., 2 H) 7.26 (d,J=8.01 Hz, 2 H) 7.61 (d, J=8.20 HZ, 2 H).

Step B)(2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(tetrahydro-2H-pyran-4-yl)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

To a flask of4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]tetrahydro-2H-pyran(98.3 mg, 0.341 mmol) and(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2B, (170 mg, 0.341 mmol) wasadded Pd(II)Encat (113 mg, 0.034 mmol, 10 mol %) followed by dioxane(5.0 mL) and 2.0 M potassium carbonate (0.511 mL). The reaction mixturewas stirred for overnight at 80° C. The reaction mixture was cooled andpoured onto celite. The filtered solution was concentrated under reducedpressure. The residue was purified by chromatography on silica gel(Gradient: 0% to 100% ethyl acetate in heptane) to give the titlecompound as a glass (82 mg, 45%). LCMS m/z 533.0 (M+1). ¹H NMR (400 MHz,METHANOL-d₄) δ ppm 1.61 (br. s., 2 H) 1.73 (d, J=7.23 Hz, 3 H) 1.75-1.89(m, 1 H) 1.75-1.89 (m, 6 H) 2.40 (dddd, J=13.35, 10.86, 7.91, 5.18 Hz, 1H) 2.54-2.68 (m, 1 H) 2.82-2.93 (m, 1 H) 3.10-3.15 (m, 3 H) 3.54-3.64(m, 3 H) 3.91-4.02 (m, 1 H) 4.02-4.07 (m, 2 H) 4.14-4.24 (m, 1 H)4.24-4.36 (m, 1 H) 5.05 (d, J=2.34 Hz, 1 H) 6.74-6.81 (m, 2 H) 7.39 (m,J=8.40 Hz, 2 H) 7.65 (m, J=8.20 Hz, 2 H) 7.71 (dd, J=6.74, 5.76 Hz, 1 H)7.71 (dd, J=6.74, 5.76 Hz, 1 H).

Step C)(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(tetrahydro-2H-pyran-4-yl)phenyl]pyridin-1(2H)-yl}butanamide

To a solution of(2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(tetrahydro-2H-pyran-4-yl)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(82 mg, 0.15 mmol) in 2-propanol (1.5 mL) was added 1.0 N hydrochloricacid (0.77 mL). The solution was stirred for 1 h. The reaction wasconcentrated, the residue was triturated with 2-propanol as a whitesuspension at 50° C. for 30 minutes. A white solid was collected byfiltration (75%). LCMS m/z 449.0 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δ ppm1.57 (s, 3 H) 1.65-1.74 (m, 4 H) 2.11-2.21 (m, 1 H) 2.37-2.47 (m, 1 H)2.83 (tt, J=10.40, 5.42 Hz, 1 H) 3.11 (s, 3 H) 3.39-3.49 (m, 2 H) 3.74(td, J=12.01, 4.69 Hz, 1 H) 3.92-3.99 (m, 2 H) 4.11 (td, J=11.91, 5.08Hz, 1 H) 6.65 (dd, J=7.03, 2.15 Hz, 1 H) 6.69 (d, J=2.15 Hz, 1 H) 7.37(m, 2 H) 7.67 (m, 2 H) 7.74 (d, J=7.23 Hz, 1 H) 9.27 (br. s., 1 H) 11.19(s, 1 H).

Example 48(2R)-N-hydroxy-4-[4-{4-[(2-methoxyethyl)thio]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

Step A)2-{4-[(2-Methoxyethyl)thio]phenyl}-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

The title compound was produced by following the general methodology ofExample 47, Step A, using 1-bromo-4-[(2-methoxyethyl)thio]benzene (250mg, 1.01 mmol.) in place of 4-(4-bromophenyl)tetrahydro-2H-pyran. Thetitle compound was obtained an oil (67.5%). ¹H NMR (400 MHz, DMSO-d₆) δppm 1.28 (s, 12 H) 3.18 (t, J=6.45 Hz, 2 H) 3.25 (s, 3 H) 3.52 (t,J=6.45 Hz, 2 H) 7.31 (d, J=8.40 Hz, 2 H) 7.31 (d, J=4.88 Hz, 1 H) 7.58(d, J=8.40 Hz, 2 H)

Step B)(2R)-4-[4-{4-[(2-methoxyethyl)thio]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

The title compound was produced by following the general methodology ofExample 47, Step B, giving the title compound as a solid (66.8%). LCMSm/z 539.0 (M+1).

Step C)(2R)-N-hydroxy-4-[4-{4-[(2-methoxyethyl)thio]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

The title compound was produced by following the general methodology ofExample 47, Step C, producing a white solid that was collected byfiltration (64%). LCMS m/z 455.0 (M+1). ¹H NMR (400 MHz, DMSO-d6) δ ppm1.57 (s, 3 H) 2.16 (ddd, J=12.65, 6.20, 5.96 Hz, 1 H) 3.11 (s, 3 H) 3.22(t, J=6.45 Hz, 2 H) 3.26 (s, 3 H) 3.54 (t, J=6.45 Hz, 2 H) 3.74 (td,J=12.01, 5.08 Hz, 1 H) 4.11 (td, J=11.91, 5.08 Hz, 1 H) 6.67 (dd,J=7.13, 2.05 Hz, 1 H) 6.71 (d, J=1.95 Hz, 1 H) 7.41 (d, J=8.59 Hz, 2 H)7.68 (d, J=8.59 Hz, 2 H) 7.76 (d, J=7.03 Hz, 1 H)

Example 49A(2R)-4-[4-(4-chloro-2,3-difluorophenvyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A:2-(4-chloro-2,3-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

To a solution of 1-bromo-4-chloro-2,3-difluorobenzene (720 mg, 3.17mmol) in tetrahydrofuran (10 mL) was added i-propylmagesiumchloride(1.90 mL, 3.80 mmol) at 0° C. The reaction mixture was stirred at 0° C.for 1 h. Then 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxa-borolane(0.98 mL, 4.75 mmol) in tetrahydrofuran (5.0 mL) was added. The reactionmixture was allowed to warm up to room temperature and stirred at RT for1 h. The mixture was used directly in the next step.

Step B:(2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoicacid

Into the THF solution of2-(4-chloro-2,3-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(771 mg, 2.81 mmol) was added 1.0 M K₃PO₄ (7.02 mL), ethyl(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate(1000 mg, 2.34 mmol) and Pd(II)dppf.DCM (90 mg, 0.117 mmol, 5 mol %).The reaction mixture was stirred for 1 h at 65° C. To the reactionmixture was then added a solution of LiOH (168 mg, 7.02 mmol) in water(7.5 mL). The reaction mixture was stirred for 45 min at 55° C. Thereaction mixture was treated with 1 N NaOH (4 mL) and the aqueous layerwas separated and adjusted to a pH of 2 with 3 N HCl. A precipitateformed and was collected by filtration and washed with EtOAc to give thetitle compound as an off-white solid (0.88 g, 89.6%) LCMS m/z 420.0(M+1). ¹H NMR ppm 1.58 (s, 3 H) 2.20 (ddd, J=13.12, 10.68, 4.88 Hz, 1 H)2.40-2.48 (m, 1 H) 3.17 (s, 3 H) 3.95 (ddd, J=12.54, 10.88, 5.66 Hz, 1H) 4.10 (ddd, J=12.63, 10.78, 4.88 Hz, 1 H) 6.47 (dt, J=7.02, 1.85 Hz, 1H) 6.58-6.61 (m, 1 H) 7.42-7.49 (m, 1 H) 7.52-7.58 (m, 1 H) 7.81 (d,J=7.02 Hz, 1 H).

Step C:(2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

To a suspension of(2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoicacid (4500 mg, 10.7 mmol) in Me-THF (450 mL) was added N-methylmorpholine (1.80 mL, 16.1 mmol) and2-chloro-4,6-dimethoxy-1,3,5-triazine (2520 mg, 13.9 mmol). The reactionmixture was stirred at room temperature for 1 h. To the mixture wasadded O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (1630 mg, 13.9 mmol) andthe resulting mixture was stirred at room temperature for 1 h. Thereaction mixture was washed with water and passed through pad of sodiumsulfate, celite and silica gel. The pad was washed with ethyl acetate.The combined organic solution was concentrated under reduced pressure togive the title compound as a solid in quantitative yield. LCMS m/z 519.0(M+1). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.48-1.57 (m, 3 H) 1.59 (d,J=3.90 Hz, 3 H) 1.64-1.74 (m, 3 H) 2.15-2.26 (m, 1 H) 2.39-2.49 (m, 1 H)3.10 (d, J=6.44 Hz, 3 H) 3.46-3.58 (m, 1 H) 3.70-3.83 (m, 1 H) 4.03 (d,J=7.02 Hz, 1 H) 4.07-4.21 (m, 1 H) 4.95-5.01 (m, 1 H) 6.48-6.53 (m, 1 H)6.61-6.64 (m, 1 H) 7.42-7.49 (m, 1 H) 7.51-7.59 (m, 1 H) 7.79 (dd,J=10.83, 7.12 Hz, 1 H), H—N wasn't observed. ¹⁹F NMR (376 MHz, DMSO-d₆)δ ppm −138.09 (dd, J=22.56, 7.52 Hz) −139.10 (dd, J=22.56, 7.52 Hz)

Step D:(2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

To a heterogeneous mixture of(2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(14500 mg, 26.94 mmol) in Ethanol (50 mL) and water (100 mL) was added asolution of PPTS (pyridinium p-touluenesulfonate) (7090 mg, 27.9 mmol).The mixture was stirred overnight at 70° C. and a solid formed. Thesolid was collected via filtration and dried to furnish the titlecompound as a white solid (5.7 g, 46.9%). The filtrate was concentratedto half the volume and more desired product formed and was collected viafiltration to provide additional title compound (3.3 g, 27.1%). LCMS m/z435.0 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.55 (s, 3 H) 2.06-2.20 (m,1 H) 2.36-2.45 (m, 1 H) 3.08 (s, 3 H) 3.67-3.81 (m, 1 H) 4.10 (ddd,J=12.20, 11.32, 4.78 Hz, 1 H) 6.47 (dt, J=7.17, 1.98 Hz, 1 H) 6.57-6.62(m, 1 H) 7.39-7.47 (m, 1 H) 7.49-7.57 (m, 1 H) 7.77 (d, J=7.22 Hz, 1 H)9.23 (br. s., 1 H) 11.08 (s, 1 H) ¹⁹F NMR (376 MHz, DMSO-d₆) δ ppm−138.08 (dd, J=22.56, 7.52 Hz)-139.09 (dd, J=22.56, 7.52 Hz).

Example 49B Alternative Preparation of(2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

The title compound was made via a sequential procedure comprised ofborylation, Suzuki coupling and THP removal. This one pot method couldreadily be applied to other compounds of the invention.

To a THF solution of 4-chloro-2,3-difluorophenyl bromide (1.0 mmol, 227mg in 3 mL) at 0° C. was added 1.1 eq. i-PrMgBr (2.0 M in THF, 0.55 mL)slowly over 5 min. The resulting mixture was stirred at 0° C. for 30min. To the reaction mixture was added2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.1 mmol, 204 mg)under N₂. The resulting mixture was stirred at 0° C. for 5 min and thenRT for 30 min. LCMS indicated all bromide starting material wasconsumed. In a separate flask was added(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(T6), which may be produced as in Preparation 2 B, (1.0 mmol, 500 mg),K₂CO₃ (3.0 mmol, 420 mg), 3 mL DMF and 0.3 mL water. The boronate r×nmixture was then added into this flask. The mixture was deoxygenated bybubbling N₂ through for 10 min. Pd EnCat™ (0.15 equiv., 0.15 mmol, 460mg) was added and bubbled with N₂ for an additional 5 mins. The reactionmixture was stirred at 80° C. for 16 h under N₂ and turned into a blackdry solid. LCMS indicated 54% coupled product, m/z 519.3 (M+1), 435.2(M+1-THP) and 25% coupled product without THPm/z 435.2 (M+1). To themixture was added 8 mL DCM and 12 mL trifluoroacetic acid. Mixturestirred at RT for 1 h. LCMS indicated complete THP deprotection. Themixture was concentrated on the rotavap. The residue was treated with 6mL DMSO, loaded onto a 5 g C18 pre-column, and purified using a 25 g C18column with 0 to 80% ACN in water with 0.1% formic acid at a flow rateof 25 mL/min in 50 CV. The combined fractions furnished an off whitesolid, 257 mg (59%).

Example 50(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2,3,4-trifluorophenyl)pyridin-1(2H)-yl]butanamide

The title compound was produced by following the general methodology ofExample 21, Step A through C using 2,3,4-trifluorophenylboronic acidinstead of (2-Fluoro-4-methoxyphenyl)boronic acid with comparableyields. MS (LCMS) m/z 419.0 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.54(s, 3 H) 2.09-2.18 (m, 1 H) 2.37-2.45 (m, 1 H) 3.07 (s, 3 H) 3.68-3.78(m, 1 H) 4.04-4.14 (m, 1 H) 6.43-6.48 (m, 1 H) 6.57 (s, 1 H) 7.36-7.49(m, 2 H) 7.76 (d, J=7.08 Hz, 1 H) 9.21 (br. s., 1 H) 11.08 (s, 1 H).

Example 514-[4-(Benzyloxy)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A)4-[4-(Benzyloxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoate

To a solution of ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate (345mg, 1.20 mmol) and 4-(benzyloxy)pyridin-2-ol (201 mg, 1.00 mmol) intetrahydrofuran (10 mL) was added cesium carbonate (652 mg, 2.00) atambient temperature. The resulting mixture was stirred at 50° C.overnight. The mixture was allowed to cool to ambient temperature andfiltered through a celite pad. The pad was washed with ethyl acetate;the filtrates were combined and concentrated to a crude residue. Thematerial was purified via filtration through a silica gel pad and elutedwith heptanes/ethyl acetate. The desired fractions were isolated and thesolvent removed via rotary evaporation affording ethyl4-[4-(benzyloxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoateas a white solid. 302.2 mg. ¹H NMR (CD₃OD) 7.47, (1H, d), 7.41-7.29 (5H,m), 6.15-6.13, (1H, dd), 5.96 (1H, d), 5.07 (2H, s), 4.20-4.12 (2H, m),4.00-3.93 (1H, m), 3.47 (1H, q), 3.21 (3H, s), 2.60-2.53 (1H, m),2.32-2.25 (1H, M), 3.20 (3H, s), 1.26 (3H, t) ppm.

Step B)4-[4-(Benzyloxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoic acid

To a solution of ethyl4-[4-(benzyloxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoate(740 mg, 1.82 mmol) in tetrahyrofuran/methanol/water (4:1:1, 18.2 mL)was added lithium hydroxide monohydrate (152 mg, 3.63 mmol). The mixturewas stirred at ambient temperature overnight. The mixture was dilutedwith aqueous HCl (1N in water) and extracted with ether 2×. The combinedorganic extracts were washed with water, dried over magnesium sulfate,filtered and concentrated to dryness to afford4-[4-(benzyloxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoicacid as a solid. 674.9 mg.

LCMS: (M+1) 380

Step C)4-[4-(Benzyloxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

To a solution of4-[4-(benzyloxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoicacid (670 mg, 1.77 mmol) in methylene chloride (18 mL) at ambienttemperature was added 1,(3-dimethylaminopropyl)-3-ethylcarbodiimidehydrochloride (474 mg, 2.47 mmol), 1-hydroxy benzotriazole monohydrate(487 mg, 3.18 mmol), triethylamine (443 uL, 3.18 mmol) andO-tetrahydro-2H-pyran-2-yl-hydroxylamine (310 mg, 2.65 mmol). Theresulting mixture was stirred at ambient temperature overnight. Themixture was diluted with methylene chloride and water. The phases wereseparated and the aqueous layer was extracted with methylene chloridetwo times. The organic extracts were combined and dried over magnesiumsulfate, filtered and concentrated to a crude residue. The crude residuewas purified via silica gel chromatography eluting with methylenechloride and methanol. The fractions containing desired product werecombined and concentrated to afford4-[4-(benzyloxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideas an oil. 536.3 mg

LCMS: (M−1) 477.3

Step D)4-[4-(Benzyloxy)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

4-[4-(Benzyloxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(536.3 mg, 1.12 mmol) was dissolved in methylene chloride (5 mL) atambient temperature. To this solution was added HCl (4M in 1,4-dioxane,8.41 mL, 30 mmol) and the slurry was stirred at RT for 15 minutes.Methanol (1 mL) was added followed by silica gel and the mixture wasconcentrated to dryness. The crude material purified via silica gelchromatography eluting with methylene chloride/methanol to afford titlecompound as a solid 117.8 mg. LCMS: (M+1) 395.3 ¹H NMR (CD₃OD) 7.51 (1H,d, J=7.62 Hz), 7.42-7.32 (5H, m), 6.18 (1H, dd, J=7.42, J=2.73), 5.09(2H, s), 4.21-4.13 (1H, m), 3.85-3.77 (1H, m), 3.08 (3H, s), 2.53-2.45(1H, m), 2.32-2.25 (1H, m), 1.65 (3H, s) ppm.

Example 52N-Hydroxy-2-methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanamide

Step A) 4-Iodo-3-methylpyridin-2(1H)-one

To a solution of 2-fluoro-4-iodo-3-methylpyridine (1.68 g, 7.09 mmol) in1,4-dioxane/water (1:1, 5.2 mL) was added concentrated HCl (5.5 mL). Theresulting clear solution was heated to 100° C. After 1 h, the reactionmixture was allowed to cool to ambient temperature and was stirredovernight, during which time a precipate formed. The mixture wasfiltered and dried to a constant weight to afford4-iodo-3-methylpyridin-2(1H)-one as a yellow solid 1.47 g.

Step B)4-(4-Iodo-3-methyl-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

To a solution of ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate(2.08 g, 7.25 mmol) and 4-iodo-3-methylpyridin-2(1H)-one (1.42 g, 6.04mmol) in tetrahydrofuran (60.4 mL) was added cesium carbonate (4.06 g,12.1) at ambient temperature. The resulting mixture was stirred at 50°C. overnight. The mixture was allowed to cool to ambient temperature andfiltered through a celite pad. The pad was washed with ethyl acetate andthe filtrate was concentrated to a crude residue. The material waspurified via filtration through a silica gel pad, eluting withheptanes/ethyl acetate. The desired fractions were isolated, the solventremoved via rotary evaporation affording ethyl4-(4-iodo-3-methyl-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoateas an oil. 1.97 g

LCMS: (M+1) 442

Step C) Ethyl2-methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanoate

Water (1 mL) was added to a suspension of potassium carbonate (392 mg,2.84 mg), phenylboronic acid (76.1 mg, 0.624 mmol), and ethyl4-(4-iodo-3-methyl-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate(250 mg, 0.567 mmol) in 1,4-dioxane (5 mL) at ambient temperature. Tothis mixture was added Pd EnCat™ (154 mg, 0.06 mmol) and the mixture wasstirred at 80° C. overnight. The mixture was cooled to ambienttemperature, filtered, diluted with ethyl acetate and washed with water.To the organic extract was added silica gel and the mixture wasconcentrated to dryness. The material was purified via silica gelchromatography eluting with ethyl acetate/heptanes to afford ethyl2-methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanoateas an oil. 118.3 mg

LCMS: (M+1) 392.3

Step D)2-Methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanoic acid

To a solution of ethyl2-methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanoate(118.3 mg, 0.313 mmol) in tetrahydrofuran/methanol/water (4:1:1, 3.13mL) was added lithium hydroxide monohydrate (26.3 mg, 0.626 mmol). Themixture was stirred at ambient temperature overnight. The mixture wasdiluted with aqueous HCl (1N in water) and extracted with ethyl acetate2×. The combined organic extracts were dried over magnesium sulfate,filtered and concentrated to dryness to afford2-methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanoicacid as a solid. 109.4 mg.

LCMS: (M+1) 364.3

Step E)2-methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

To a solution of2-methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanoicacid (109.4 mg, 0.301 mmol) in methylene chloride (3 mL) at ambienttemperature was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimidehydrochloride (80.7 mg, 0.421 mmol), 1-hydroxy benzotriazole monohydrate(83 mg, 0.542 mmol), triethyl amine (75 uL, 0.542 mmol) andO-tetrahydro-2H-pyran-2-yl-hydroxylamine (53 mg, 0.452 mmol). Theresulting mixture was stirred at ambient temperature overnight. Themixture was diluted with methylene chloride and washed successively withsat.aqueous sodium bicarbonate, aqueous HCl (1 N) and water. The organicextracts were dried over magnesium sulfate, filtered and concentrated toa crude residue. The crude residue was purified via silica gelchromatography eluting with methylene chloride and methanol. Thefractions containing the desired product were combined and concentratedto afford2-methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideas a solid. 137.3 mg

LCMS: (M−1) 477.3

Step F)N-hydroxy-2-methyl-4-(3-methyl-2-oxo-4-phenylpridin-1(2H)-yl)-2-(methylsulfonyl)butanamide

2-methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(137 mg, 0.296 mmol) was dissolved in methylene chloride (2 mL) atambient temperature. To this solution was added HCl (4M in 1,4-dioxane,2.22 mL, 8.88 mmol) and the slurry was stirred at ambient temperaturefor 15 minutes. Methanol (1 mL) was added followed by silica gel and themixture was concentrated to dryness. Crude material was purified viasilica gel chromatography eluting with methylene chloride/methanol toaffordN-hydroxy-2-methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanamideas a solid. 65.8 mg

LCMS: (M+1) 379.3

¹H NMR (CD₃OD) 7.52 (1H, d, J=7.03 Hz), 7.47-7.38 (3H, m), 7.33-7.30(2H, m), 6.32 (1H, d, J=6.83), 4.34-4.27 (1H, m), 3.95-3.88 (1H, m),3.10 (3H, s), 2.61-254 (1H, m), 2.41-2.34 (1H, m), 2.03 (3H, s), 1.70(3H, s) ppm.

Example 534-(4-Cyclohexyl-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Step A)4-(4-Cyclohexyl-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

A solution of cyclohexylmagnesium bromide (1.0M sol in THF, 1.6 mL, 1.56mmol) was added to a suspension of copper (I) bromide-DMS complex in 6mL THF at −78° C. under N₂. The mixture was warmed to room temperatureuntil a dark colored solution was observed (ca 15 min) then re-cooled to−78° C. A suspension of4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,which may be produced as in Preparation 2A (249 mg, 0.5 mmol) in THF (6mL) was added to the mixture. The resulting mixture was stirred at −78°C. for 2 hours then warmed to room temperature. The reaction mixture wasquenched with sat. aq. NH₄Cl (6 mL) and diluted with water (60 mL) andextracted with ethyl acetate (2×60 mL). The combined organics werewashed with water 100 mL and brine 100 mL, and dried over sodiumsulfate, filtered and concentrated in vacuo to furnish 300 mg crude oil.The crude material was purified by chromatography on silica gel(gradient: 100:0 heptanes:ethyl acetate to 0:100 heptane:ethyl acetate)to afford a clear oil (274 mg, 96%) as a mixture of unreacted startingmaterial and title compound.

Step B)4-(4-Cyclohexyl-2-oxopyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

A 4.0 M solution of HCl in 1,4-dioxane (3.3 mL) was added slowly to asolution of the4-(4-cyclohexyl-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(220 mg, 0.14 mmol) in dichloromethane (5 mL) followed by methanol (1mL) at room temperature. The reaction was concentrated in vacuo and thetitle compound was purified using reverse phase chromatography (Gradientused with formic acid modifier(0.05%), 95:5 water:acetonitrile to 5:95water:acetonitrile). Gradient time 6 minutes. Furnished a white solid(105 mg, 58.6%) MS (LC/MS) m/z 371.6 (M+1)

Example 542-Ethyl-N-hydroxy-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanamide

Step A) Ethyl 2-(methylsulfonyl)butanoate

Ethyl(methylsulfonyl)acetate (0.79 mL, 5.8 mmol, 1.0 equiv) was addeddropwise via syringe to a mixture of sodium hydride (0.25 g 60% inmineral oil, 6.1 mmol, 1.1 equiv) in DMF (20 mL) at room temperature.The mixture was allowed to stir for 30 min, after which time1-iodoethane (0.48 mL, 5.8 mmol, 1.0 equiv) was added. The reaction wasallowed to stir overnight. A solution of saturated ammonium chloride (10mL) and water (10 mL) were added, and the resulting mixture wasextracted with diethyl ether (1×25 mL). The organic phase was separated,washed with water (1×10 mL), brine (1×5 mL), dried over anhydrousmagnesium sulfate, and concentrated under reduced pressure. The crudematerial was purified by flash chromatography (2:1-0:1 heptane/ethylacetate) to provide a white solid (0.29 g, 26%). MS (LCMS) m/z 195.4(M+1). ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.05 (t, J=7.41 Hz, 3 H)1.33 (t, J=7.12 Hz, 3 H) 1.99-2.25 (m, 2 H) 2.99 (s, 3 H) 3.66 (dd,J=10.54, 3.90 Hz, 1 H) 4.30 (q, J=7.22 Hz, 2 H).

Step B) Ethyl 4-bromo-2-ethyl-2-(methylsulfonyl)butanoate

Sodium hydride (66 mg, 1.6 mmol, 1.05 equiv) was added to a solution ofthe ethyl 2-(methylsulfonyl)butanoate (0.29 g, 1.5 mmol, 1.0 equiv) inDMF (5 mL) at room temperature. After 30 min, 1,2-dibromopropane (0.42g, 2.2 mmol, 1.5 equiv) was added, and the reaction was allowed to stirovernight. Water (5 mL) was added, and the resulting mixture wasextracted with diethyl ether (1×20 mL). The organic phase was separated,washed with brine (1×5 mL), dried over anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. The crude material waspurified by flash chromatography on silica gel (2:1-1:1 heptane/ethylacetate) to provide a colorless oil (0.17 g, 37%). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.03 (t, J=7.51 Hz, 3 H) 1.33 (t, J=7.12 Hz, 3 H)1.97-2.23 (m, 2 H) 2.54 (ddd, J=14.63, 12.20, 5.17 Hz, 1 H) 2.76 (ddd,J=14.63, 12.10, 4.68 Hz, 1 H) 3.06 (s, 3 H) 3.50-3.61 (m, 1 H) 3.69(ddd, J=12.20, 9.76, 4.59 Hz, 1 H) 4.31 (q, J=7.02 Hz, 2 H).

Step C) Ethyl2-ethyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoate

Cesium carbonate (0.71 g, 2.2 mmol, 4.0 equiv) was added to a solutionof the 4-phenylpyridin-2-ol (0.10 g, 0.58 mmol, 1.05 equiv) and ethyl4-bromo-2-ethyl-2-(methylsulfonyl)butanoate (0.17 g, 0.55 mmol, 1.0equiv) in tetrahydrofuran (5 mL). The resulting mixture was heated to55° C. and allowed to stir for 3 days. The reaction was diluted withethyl acetate (20 mL), filtered through a pad of Celite, andconcentrated under reduced pressure. The crude material was purified byflash chromatography on silica gel (4:1-0:1 heptane/ethyl acetate) toprovide a light yellow oil (43 mg, 20%). ¹H NMR (400 MHz, CHLOROFORM-d)δ ppm 1.15 (t, J=7.42 Hz, 3 H) 1.33 (t, J=7.13 Hz, 3 H) 2.07-2.19 (m, 1H) 2.26-2.36 (m, 1 H) 2.44 (ddd, J=14.89, 11.18, 4.98 Hz, 1 H) 2.59-2.71(m, 1 H) 3.15 (s, 3 H) 4.19-4.37 (m, 4 H) 6.45 (dd, J=7.03, 1.56 Hz, 1H) 6.72-6.78 (m, 1 H) 7.38-7.48 (m, 4 H) 7.53-7.60 (m, 2 H).

Step D)2-Ethyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoicacid

Potassium hydroxide (37 mg, 0.66 mmol, 6.0 equiv) was added to asolution of ethyl2-ethyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoate(43 mg, 0.11 mmol, 1.0 equiv) in 2:2:1 tetrahydrofuran-methanol-water(2.5 mL) at 0° C. The reaction was allowed to warm to room temperatureand stir overnight. The reaction was concentrated under reduced pressureto provide a wet residue that was diluted with water (5 mL) andacidified (to pH=2) with 1.0 hydrochloric acid. The resulting whiteprecipitate was filtered, washed with water, and dried under reducedpressure to provide the title compound (34 mg, 85%). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.09 (t, J=7.52 Hz, 3 H) 1.42 (s, 3 H) 1.93-2.07 (m,1 H) 2.23-2.37 (m, 2 H) 2.55 (d, J=5.66 Hz, 1 H) 3.25 (s, 3 H) 4.10-4.24(m, 2 H) 4.47-4.59 (m, 2 H) 6.63-6.67 (m, 1 H) 6.90 (d, J=1.95 Hz, 1 H)7.44-7.50 (m, 4 H) 7.54-7.62 (m, 2 H).

Step E)2-Ethyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Diisopropylethylamine (35 uL, 0.2 mmol, 2.1 equiv) and 1-hydroxylbenzotriazole monohydrate (27 mg, 0.18 mmol, 1.9 equiv) were addedsequentially to a solution of2-ethyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoicacid (34 mg, 0.09 mmol, 1.0 equiv) in dichloromethane (2 mL) at roomtemperature. After 30 min, O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (15mg, 0.12 mmol, 1.3 equiv) andN-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (26 mg,0.13 mmol, 1.4 equiv) were added, and the reaction was allowed to stirovernight. Water (2 mL) was added, the organic phase was separated,dried over anhydrous magnesium sulfate, and concentrated under reducedpressure. The crude material was purified by flash chromatography(1:1-0:1 heptane/ethyl acetate) to provide a colorless oil (45 mg,100%). MS (LCMS) m/z 461.8 (M−1).

Step F)2-Ethyl-N-hydroxy-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanamide

A solution of hydrochloric acid (0.5 mL, 4.0 M in 1,4-dioxane) was addeddropwise to a solution of2-ethyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(45 mg, 0.1 mmol) in dichloromethane (0.5 mL) and methanol (0.1 mL) at0° C. After 2 h, the reaction was concentrated under reduced pressure.The resulting residue was triturated with diethyl ether, filtered,washed with heptane, and dried under reduced pressure to provide anoff-white solid (10 mg, 27%). MS (LCMS) m/z 379.5 (M+1). ¹H NMR (400MHz, CDCl₃) δ ppm 0.97 (t, J=7.5 Hz, 3H), 1.86-1.95 (m, 1H), 2.31-2.45(m, 3H), 3.29 (s, 3H), 3.99-4.08 (m 1H), 4.53-4.63 (m, 1H), 6.69 (br d,J=5.6 Hz, 1H), 6.99 (br s, 1H), 7.44-7.49 (m, 4H), 7.55-7.60 (m, 2H).

Example 55(2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A) 3-Fluoro-4-iodopyridin-2(1H)-one

2,3-Difluoro-4-iodopyridine (300 mg, 1.24 mmol) was suspended in aceticacid:water (2:1, 15 mL). The mixture was heated to reflux and stirred atthis temperature overnight. Reaction was concentrated to dryness, andtriturated in water (10 mL) for 30 min. The solid was collected viafiltration, washed with water (2×10 mL), and pentane (2×20 mL) and driedunder vacuum to afford the title compound as a white solid (354 mg,71.4%). LC-MS m/z 342.0 (M+1). ¹H NMR (400 MHz, METHANOL-d₄) δ ppm6.56-6.82 (m, 1 H) 6.83-7.18 (m, 1 H).

Step B) Ethyl(2R)-4-(3-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

Cesium carbonate (1.50 g, 4.60 mmol) was added to a solution of3-fluoro-4-iodopyridin-2(1H)-one (354 mg, 1.48 mmol) and ethyl4-bromo-2-methyl-2-(methylsulfonyl)butanoate (595 mg, 2.07 mmol in THF(25 mL). The resulting suspension was heated to 50° C. and stirredovernight. The reaction was heated to 70° C. and stirred at thistemperature overnight. The reaction was filtered through celite (−1inch), and the filter pad was washed with ethyl acetate (2×30 ml). Thecombined filtrates were concentrated and the crude was purified viaflash chromatography on an Analogix SF15-24g column and an eluant ofethyl acetate in heptane (50-100%) to afford the title compounds as aclear gum (366 mg, 55.5%). LC-MS m/z 445.9 (M+1). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.35 (t, J=7.12 Hz, 3 H) 1.76 (s, 3 H) 2.43-2.56 (m,2 H) 3.11 (s, 3 H) 3.97-4.10 (m, 1 H) 4.20-4.38 (m, 3 H) 6.50 (dd, 1 H)6.75-6.98 (m, 1 H).

Step C) Ethyl(2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

Pd EnCat™ (172 mg, 0.067 mmol) was added to a mixture of potassiumcarbonate (298 mg, 2.16 mmol), phenylboronic acid (132 mg, 1.08 mmol),and ethyl(2R)-4-(3-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate(288 mg, 0.647 mmol) in 1,4-dioxane:water (10 ml, 4:1) in a 20 ml vial.The vial was sealed and the reaction was heated to 80° C. and allowed tostir overnight at that temperature. The reaction was allowed to cool toRT, filtered and the catalyst was washed with methanol (20 mL) anddichloromethane (20 mL). The combined filtrates were concentrated andthe crude product was purified via flash chromatography using anAnalogix SF15-12g column and an eluant of ethyl acetate in heptane(60-100%) to afford the title compound as a white solid (131 mg, 51.2%).LC-MS m/z 396.1 (M+1). ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36 (t,J=7.12 Hz, 3 H) 1.79 (s, 3 H) 2.46-2.67 (m, 2 H) 3.14 (s, 3 H) 3.99-4.16(m, 1 H) 4.22-4.44 (m, 3 H) 6.24-6.39 (m, 1 H) 7.10-7.22 (m, 1 H)7.38-7.55 (m, 3 H) 7.54-7.63 (m, 2 H).

Step D)(2R)-4-(3-Fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid

Potassium hydroxide (120 mg, 2.14 mmol) was added to a solution of ethyl(2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate(131 mg, 0.33 mmol) in THF:methanol:water (2:2:1, 10 mL) and thereaction was stirred at RT overnight. The reaction was concentrated, andthe residue was dissolved in aqueous 1N sodium hydroxide (20 mL), washedwith ethyl acetate (3×20 mL), acidified using concentrated HCl, andextracted with ethyl acetate (3×50 mL). The combined organics were dried(MgSO₄), filtered, and concentrated to afford the title compound as awhite solid (88.4 mg, 72.7%). LC-MS m/z 383.0 (M+1). ¹H NMR (400 MHz,DMSO-d₆) δ ppm 1.59 (s, 3 H) 2.13-2.30 (m, 1 H) 3.17 (s, 3 H) 3.93-4.23(m, 2 H) 6.43 (t, J=6.93 Hz, 1 H) 7.44-7.56 (m, 3 H) 7.57-7.66 (m, 3 H).

Step E)(2R)-4-(3-Fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-(3-Fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid (88.4 mg, 0.241 mmol) was dissolved in anhydrous DCM (5 ml) andtreated with Hunig's Base (93 uL, 0.54 mmol) followed by HOBt (78 mg,0.51 mmol) and the solution was stirred at RT for 30 minutes. Themixture was then treated with THP-ONH₂ (46 mg, 0.39 mmol) followed byEDCI (71 mg, 0.37 mmol) and the reaction was allowed to stir at RT. Thereaction was concentrated in vacuo and the crude product was purifiedvia flash chromatography using an Analogix SF10-8g column and an eluantof ethyl acetate in heptane (50-100%) to afford the title compound as ayellow solid (110 mg, 97.9%).

LC-MS m/z 465.0 (M−1).

Step F)(2R)-4-(3-Fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Pyrinium p-toluenesulfonate (20 mg, 0.080 mmol) was added to a solutionof(2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(110 mg, 0.236 mmol) in ethanol (5 ml) and heated at reflux for 3 hours.The solution was cooled to RT, and upon cooling, a solid precipitated.The solid was collected via filtration and washed with ethanol (5 mL),heptane (10 mL), and ether (10 mL). The solid was dried under vacuum toafford the title compound as a yellow solid (38.4 mg, 42.6%). LC-MS m/z383.0 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.60 (s, 3 H) 2.10-2.26 (m,1 H) 3.11 (s, 3 H) 3.70-3.94 (m, 1 H) 4.07-4.30 (m, 1 H) 6.46 (t, J=6.93Hz, 1 H) 7.46-7.57 (m, 3 H) 7.59-7.65 (m, 3 H)

Example 56(2R)-4-(5-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A) 2,5-difluoro-4-iodopyridine

n-Butyllithium (2.5 M in hexanes, 18.6 mL, 46.5 mmol) was added to asolution of diisopropylamine (6.51 mL, 46.1 mmol) in anhydroustetrahydrofuran (85 mL) at −780C and stirred at this temperature for 1hour. A solution of 2,5-difluoropyridine (5.0 g, 43 mmol) in anhydrousTHF (12 mL) was added dropwise via cannula and the reaction was stirredat −78° C. for 3 hours. After this time, iodine (12.1 g, 47.8 mmol) intetrahydrofuran (50 mL) was added dropwise via cannula to the reactionat −78° C. and stirred at this temperature for 1 hour after completeaddition. Water (100 mL) was added to the reaction and the temperaturewas allowed to come to RT. The reaction was extracted with diethyl ether(3×100 mL). The combined organics were washed with brine (100 mL), dried(MgSO₄), filtered and concentrated. The crude was purified via flashchromatography using an Analogix SF40-80g column and an eluant of ethylacetate in heptane (0-10%) to afford the title compound as a yellowsolid (4.60 g, 44%). LC-MS m/z 242.0 (M+1). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 7.39 (t, J=3.71 Hz, 1 H) 7.96 (d, J=1.56 Hz, 1 H).

Step B) 5-Fluoro-4-iodopyridin-2(1H)-one

2,5-Difluoro-4-iodopyridine (500 mg, 2.08 mmol) was suspended in aceticacid:water (2:1, 30 mL). The mixture was heated to reflux and stirred atthis temperature overnight. The reaction was concentrated to dryness toafford the title compound as a yellow solid (491 mg, 99.0%). ¹H NMR (400MHz, DMSO-d₆) δ ppm 7.02 (d, J=5.07 Hz, 1 H) 7.69 (d, J=2.34 Hz, 1 H).

Step C) Ethyl(2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

Cesium carbonate (2.01 g, 6.16 mmol) was added to a solution of the5-fluoro-4-iodopyridin-2(1H)-one (491 mg, 2.06 mmol) and ethyl4-bromo-2-methyl-2-(methylsulfonyl)butanoate (767 mg, 2.67 mmol in THF(30 mL). The resulting suspension was heated to reflux and stirred atthis temperature overnight. The reaction was filtered through celite (−1inch), and the filter pad was washed with ethyl acetate (2×30 ml). Thecombined filtrates were concentrated and the crude was purified viaflash chromatography on an Analogix SF15-12g column and an eluant ofethyl acetate in heptane (30-100%) to afford the title compound as awhite gum (319 mg, 34.9%). LC-MS m/z 446.0 (M+1). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.35 (t, J=7.12 Hz, 3 H) 1.75 (s, 3 H) 2.40-2.58 (m,2 H) 3.10 (s, 3 H) 3.87-3.99 (m, 1 H) 4.16-4.25 (m, 1H) 4.29 (q, J=7.22Hz, 2 H) 7.15 (d, J=5.85 Hz, 1 H) 7.20 (d, J=3.32 Hz, 1 H).

Step D) Ethyl(2R)-4-(5-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

Pd EnCat™ (95 mg, 0.037 mmol) was added to a mixture of potassiumcarbonate (312 mg, 2.26 mmoll), phenylboronic acid (131 mg, 1.07 mmol),and ethyl(2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate(319 mg, 0.716 mmol) in dioxane:water (10 ml, 4:1) in a 20 mL vialequipped with a stir bar. The reaction was heated to 90° C. and allowedto stir overnight at that temperature. The reaction was allowed to coolto RT, filtered and the catalyst was washed with methanol (10 ml) anddichloromethane (10 ml). The filtrate was concentrated to afford a crudesolid. The crude was purified via flash chromatography using an AnalogixSF15-12 column and an eluant of ethyl acetate in heptane (50-100%) andmethanol in ethyl acetate (0-5%) to afford the title compound as ayellowish white solid (250 mg, 64.8%). LC-MS m/z 396.1 (M+1). ¹H NMR(400 MHz, DMSO-d₆) δ ppm 1.23 (t, J=7.12 Hz, 3 H) 1.62 (s, 3 H)2.15-2.32 (m, 1 H) 2.53-2.66 (m, 1 H) 3.16 (s, 3 H) 3.89-4.06 (m, 2 H)4.07-4.26 (m, 2 H) 6.50 (d, J=7.61 Hz, 0 H) 7.20-8.12 (m, 6 H).

Step E)(2R)-4-(5-Fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid

Ethyl(2R)-4-(5-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoatewas converted to the title product following the procedure for thepreparation of(2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid as described in Example 55, Step D. The title compound was obtainedas a white solid (171 mg, 73.6%). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.58(s, 3 H) 2.09-2.31 (m, 0 H) 2.39-2.63 (m, 1 H) 3.17 (s, 3 H) 3.83-4.19(m, 2 H) 6.49 (d, J=7.61 Hz, 1 H) 7.41-7.68 (m, 5 H) 8.06 (d, J=6.63 Hz,1 H).

Step F)((2R)-4-(5-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-(5-Fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoicacid was converted to the title product following the procedure for thepreparation of(2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideas described in Example 55, Step E. The title compound was obtained as awhite solid (197 mg, 90.9%) LC-MS m/z 465.0 (M−1).

Step G)(2R)-4-(5-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Pyridinium p-toluenesulfonate (22 mg, 0.088 mmol) was added to asolution of(2R)-4-(5-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(197 mg, 0.422 mmol). The solution was heated to reflux in ethanol (10ml) and stirred at this temperature until complete. The solution wascooled to RT, and the volatiles were removed in vacuo. The solid wastriturated in ethanol (5 mL), collected via filtration, then washed withethanol (3×5 mL), hexanes (10 mL), and ether (3×10 mL). The solid wasdried under vacuum to afford a white solid (85.1 g, 76.4%). LC-MS m/z383.1 (M+1). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.58 (s, 3 H) 2.11-2.23 (m,0 H) 2.41-2.55 (m, 1 H) 3.12 (s, 3 H) 3.73-3.84 (m, 1 H) 3.99-4.11 (m, 1H) 6.53 (d, J=7.61 Hz, 1 H) 7.41-7.73 (m, 5 H) 8.04 (d, J=6.44 Hz, 1 H)9.24 (s, 1 H) 11.10 (s, 1 H).

Example 572-(ethylsulfonyl)-N-hydroxy-2-methyl-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanamide

The title compound was prepared following analogous procedures describedwherein sodium ethyl sulfinate was used instead sodium methyl sulfinatefor the preparation of 1A to provide 2-ethanesulfonyl-propionic acidethyl ester. The title compound may then be produced by following thegeneral methodology of Example 11. MS (LCMS) m/z 379.5 (M+1). ¹H NMR(400 MHz, METHANOL-d₄) δ ppm 1.33 (t, J=7.51 Hz, 3 H) 1.72 (s, 3 H)2.34-2.46 (m, 0 H) 2.62-2.73 (m, 0 H) 3.29-3.33 (m, 2 H) 4.02-4.13 (m, 1H) 4.33-4.44 (m, 1 H) 6.98 (s, 1 H) 7.03 (d, J=7.42 Hz, 1 H) 7.47-7.54(m, 3 H) 7.68-7.75 (m, 2 H) 7.91 (d, J=7.02 Hz, 1 H).

Example 58(2R)-N-hydroxy-4-{4-[4-(4-methoxy-2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide

Step A) 2-(4-bromophenyl)-2H-1,2,3-triazole 1-oxide

Water (20 ml) was added to a flask containing glyoxal (2.0 g, 14 mmol).Hydroxylamine.HCl (958 mg, 13.8 mmol) and sodium carbonate (1.53 g, 14.5mmol) were added in one portion to the glyoxal flask (CO₂ evolutionobserved). The reaction mixture was stirred at RT for 20 minutes(reaction mixture turned yellow). Methanol (40 ml) was added to thereaction mixture and 4-bromophenyl hydrazine.HCl (3.1 g, 13.8 mmole) wasadded portionwise under ice cooling. The reaction mixture was thenstirred at rt for 30 min. Copper (II) sulfate.hexahydrate (20 g, 78mmol) was added to the reaction mixture. A water:pyridine (1:1) mixture(200 ml) was added then heated at 90° C. for 16 hours. The reactionmixture was cooled and adjusted to pH=3 with 6N HCl (approx 200 ml). Themixture was filtered through celite to remove insolubles. The celite waswashed with additional ethyl acetate (1000 ml). The organic layer wasseparated and the product extracted additionally from the aqueous layerwith EtOAc(3×250). The organic phases were combined, dried overpotassium carbonate, filtered and concentrated to approximately half thevolume. This material was then filtered through a silica pad (approx 6in). Silica was washed with an additional 300 ml of ethyl acetate. Thesolvent was then concentrated in vacuo. The crude material was purifiedby chromatography on silica gel (4:1 heptane:EtOAc to 3:1heptane:EtOAc). Concentrated fractions furnished a light tan solid (1.0g, 30% TY). MS (LC/MS) m/z 240.1 (M+1). ¹H NMR (400 MHz, CHLOROFORM-d) δppm 7.47 (d, J=0.98 Hz, 1 H) 7.65-7.69 (m, 2 H) 7.73 (d, J=0.78 Hz, 1 H)7.86-7.90 (m, 2 H)

Step B) 2-(4-bromophenyl)-2H-1,2,3-triazol-4-yl acetate

Acetyl chloride (4.71 ml, 63 mmol) was added to a flask containing2-(4-bromophenyl)-2H-1,2,3-triazole 1-oxide (500 mg, 2.08 mmol) and wasstirred at RT for 16 hours. Acetyl chloride was removed in vacuo andethyl acetate (30 ml) was added and concentrated (2×) to furnish a lightbrown solid (520 mg, 90%). MS (LC/MS) m/z 282.1 (M+1). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 2.39 (s, 3 H) 7.57-7.63 (m, 2 H) 7.84 (s, 1H)7.87-7.93 (m, 2 H)

Step C) 2-(4-bromophenyl)-2H-1,2,3-triazol-4-ol

2-(4-bromophenyl)-2H-1,2,3-triazol-4-yl acetate (520 mg, 1.84 mmol) wastreated with methanol (10 ml) and water (10 ml) followed by 1,4-dioxane(5 ml). The resulting solution was treated with lithium hydroxide (265mg, 11.1 mmol). The reaction mixture was stirred at RT for 36 hours. 1NHCl (40 ml) was added to the reaction mixture and the product wasextracted with ethyl acetate (3×100 ml). The combined organic phaseswere dried over potassium carbonate, filtered, and concentrated. Thecrude material was purified by chromatography on silica gel (4:1heptane:EtOAc 1:4 heptane:EtOAc) to furnish a light tan solid (440 mg,98% TY). MS (LC/MS) m/z 240.21 (M+1). ¹H NMR (400 MHz, CHLOROFORM-d) δppm 7.33 (s, 1 H) 7.58 (d, J=8.98 Hz, 2 H) 7.78 (d, J=8.98 Hz, 2 H).

Step D) 2-(4-bromophenyl)-4-methoxy-2H-1,2,3-triazole

2-(4-bromophenyl)-2H-1,2,3-triazol-4-ol (200 mg, 0.833 mmol) was weighedinto a 20 ml vial equipped with a septa cap. THF (10.0 ml) was added. Tothis was added cesium carbonate (814 mg, 2.5 mmol), followed by theaddition of methyl iodide (65.8 uL, 1.04 mmol) via syringe. The reactionwas heated at 60° C. for 16 hours. Water (20 ml) was added and theproduct was extracted with ethyl acetate (2×75 ml). Organic phases werecombined, dried over potassium carbonate, filtered and concentrated tofurnish a light tan solid (190 mg, 89% TY). ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 4.04 (s, 3 H) 7.30 (s, 1 H) 7.56 (d, J=8.98 Hz, 2 H)7.84 (d, J=8.98 Hz, 2 H)

Step E)4-methoxy-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2H-1,2,3-triazole

Potassium acetate (220 mg, 2.24 mmol) was added to2-(4-bromophenyl)-4-methoxy-2H-1,2,3-triazole (190 mg, 0.748 mmol),bis(pinacolato)diboron (228 mg, 0.898 mmol) and Pd(dppf)C₂.DCM complex(185 mg, 0.224 mmol) in a 20 ml vial equipped with a septa cap. The vialwas evacuated and backfilled with nitrogen 3×. To this was added1,4-dioxane (8 ml). The reaction mixture was heated at 80° C. for 16hours. The reaction mixture was filtered through celite (approx 2inches). The celite was washed with additional ethyl acetate (150 ml).The filtrate was concentrated in vacuo and the crude material waspurified by chromatography on silica gel (9:1 heptane:1EtOAc to 2:4heptane:EtOAc) to furnish a light tan solid (145 mg, 65% TY). MS (LC/MS)m/z 302.3 (M+1). ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.37 (s, 12 H)4.06 (s, 3 H) 7.31 (s, 1 H) 7.90 (s, 2 H) 7.95 (s, 2 H).

Step F)(2R)-4-{4-[4-(4-methoxy-2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Pd EnCat (98 mg, 0.03 mmol) was added to a mixture of potassiumcarbonate (171 mg, 1.24 mmol),4-methoxy-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2H-1,2,3-triazole(138 mg, 0.457 mmol) and(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewhich may be produced as in Preparation 2B(T6) (190 mg, 0.381 mmol) indioxane:water (6 ml, 5:1mix) in a 20 ml vial. The reaction was cooledand filtered through celite (approx 1 inch). The celite was washed withadditional methanol (100 ml). The filtrate was concentrated in vacuo andthe crude material was purified by chromatography on silica gel(4:1heptane:EtOAc to 100% EtOAc to 85% EtOAc:15% methanol) to furnish alight tan gum (120 mg, 58% TY). MS (LC/MS) m/z 546.2 (M+1). ¹H NMR (400MHz, METHANOL-d₄) δ ppm 1.28 (s, 1 H) 1.57-1.70 (m, 2 H) 1.68-1.81 (m, 3H) 1.78-1.92 (m, 3 H) 2.36-2.50 (m, 1 H) 2.55-2.72 (m, 1 H) 3.09-3.21(m, 3 H) 3.56-3.70 (m, 1 H) 4.07 (s, 3 H) 4.12 (d, J=7.22 Hz, 2 H)4.15-4.25 (m, 1 H) 4.25-4.42 (m, 1 H) 5.01-5.14 (m, 1 H) 6.76-6.85 (m, 1H) 6.87 (s, 1 H) 7.49 (s, 1 H) 7.68-7.80 (m, 1 H) 7.85 (d, J=9.17 Hz, 2H) 8.08 (d, J=8.98 Hz, 2 H)

Step G)(2R)-N-hydroxy-4-{4-[4-(4-methoxy-2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide

To(2R)-4-{4-[4-(4-methoxy-2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(120 mg, 0.22 mmol) was added dioxane (2 ml), dichloromethane (2 ml),and water (1 ml). The reaction flask was cooled externally with ice thentreated with a 4.0M sol of HCl in dioxane (0.55 ml). The reactionmixture was stirred for 15 minutes then concentrated under reducedpressure. IPA (10 ml) was added and concentrated to azeotrope anyremaining water to furnish a tan solid (80 mg, 80% TY). MS (LC/MS) m/z462.3 (M+1). ¹H NMR (400 MHz, METHANOL-d₄) δ ppm 1.74 (s, 3 H) 2.34-2.51(m, 1 H) 2.55-2.81 (m, 1 H) 3.13 (s, 3 H) 3.96-4.06 (m, 1 H) 4.07 (s, 3H) 4.26-4.45 (m, 1 H) 6.84-7.00 (m, 2 H) 7.49 (s, 1 H) 7.75-7.93 (m, 3H) 8.09 (d, J=8.78 Hz, 2 H)

Example 59(2R)-4-[4-{4-[(6-methoxypyridin-3-yl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Step A: (6-methoxypyridin-3-yl)methanol

Sodium borohydride (11.30 g, 299 mmol) was added to a solution of themethyl 6-methoxynicotinate (5.00 g, 29.9 mmol) in ethanol (100 mL) at 0°C. The reaction was allowed to warm to room temperature and stirred for3 days. The reaction was cooled to 0° C. and quenched by slow additionof 1 N HCl until pH 4.0. The reaction mixture was concentrated to removeethanol. The remaining aqueous solution was washed with ethyl acetate(2×), then neutralized with saturated aqueous sodium bicarbonate, thenextracted with ethyl acetate (3×). The organic layers were combined,washed with brine, dried (Na₂SO₄), filtered and concentrated. The crudematerial was purified by silica chromatography (hexanes/ethyl acetate1:1, 3:7) to give a clear oil. Mass/Yield-3.9 g/94% TLC (hexanes/ethylacetate=1:1) Rf=0.22, UV active. ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm3.91 (s, 3 H) 4.61 (s, 2 H) 6.68-6.77 (m, 1 H) 7.49-7.68 (m, 1 H) 8.09(s, 1 H).

Step B: 5-[(4-bromophenoxy)methyl]-2-methoxypyridine

4-Bromophenol (1.37 g, 7.90 mmol) was added to a solution of(6-methoxypyridin-3-yl)methanol (1.0 g, 7.16 mmol) in THF (100 mL).Triphenylphosphine (1.88 g, 7.19 mmol) was added followed bytriethylamine (0.727 g, 7.19 mmol). The resulting solution was cooled to0° C. and DIAD (1.45 g, 7.19 mmol) was added by drop-wise addition andwas maintained at 0° C. for 30 minutes, then warmed to room temperatureand stirred for two days. The reaction was quenched by addition of waterand extracted with ether (2×100 mL). The organic layer was washed withwater (2×100 mL) then brine (1×100 mL), dried (MgSO₄), filtered andconcentrated to give a yellow oil. The crude material was purified byflash column chromatography on a Biotage SNAP cartridge Kp-sil 100gcolumn (hexanes/ethyl acetate 9:1) to give a white solid.Mass/Yield—1.78 g/84% TLC (hexanes/ethyl acetate=8:2) Rf=0.12, UVactive. LCMS MS ES+294.4/296.4. ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm3.93 (s, 3 H) 4.93 (s, 2 H) 6.72-6.78 (m, 1 H) 6.81-6.86 (m, 2 H)7.33-7.42 (m, 2 H) 7.58-7.65 (m, 1 H) 8.18 (s, 1 H).

Step C2-methoxy-5-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}pyridine

A solution of the 5-[(4-bromophenoxy)methyl]-2-methoxypyridine (0.50 g,1.70 mmol), bis(pinacolato)diborane (0.518 g, 2.04 mmol), potassiumacetate (0.698 g, 7.12 mmol) and palladium dppf (69.4 mg, 0.085 mmol) in1,4-dioxane (10 mL) was heated to reflux overnight. After 18 hours thereaction was cooled to room temperature then concentrated. The residuewas partitioned between ether and water, an emulsion was removed byfiltration through celite eluting with ether. The layers in the filtratewere separated. The organic layer was washed with water (2×) then brine(1×). The organic layer was dried (Na₂SO₄), filtered and concentrated.The crude material was purified by silica chromatography (hexanes/ethylacetate 9:1) to give a white solid. Mass/Yield—285 mg/50% LCMS MS ES+342.6. ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.32 (s, 12 H) 3.93 (s, 3H) 4.99 (s, 2 H) 6.72-6.78 (m, 1 H) 6.91-6.98 (m, 2 H) 7.61-7.69 (m, 1H) 7.71-7.79 (m, 2 H) 8.20 (s, 1 H)

Step D(2R)-4-[4-{4-[(6-methoxypyridin-3-yl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Water (1.0) was added to a suspension of potassium carbonate (222 mg,1.61 mmol),(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,T6,(400 mg, 0.803 mmol), which may be produced as in Preparation 2B and2-methoxy-5-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}pyridine(274 mg, 0.803 mmol) in 1,4-dioxane (10 mL). Pd EnCat™ (218 mg, 0.085mmol) was added and the resulting suspension was heated to 100° C. for 2hours. The reaction mixture was cooled to room temperature, then dilutedwith ethyl acetate (50 mL) and filtered through celite and washed withethyl acetate (50 mL). The filtrate was concentrated in vacuo and theresidue was partitioned between ethyl acetate 1:1 saturated brine/water.The layers were separated and the aqueous layer was extracted with ethylacetate (2×). The organic layers were combined, dried (Na₂SO₄), filteredand concentrated. The crude material was purified by silicachromatography (hexanes/ethyl acetate 1:1-05:95) to give a white solid.Mass/Yield —254 mg/54% LCMS (MS ES−) 584.8. ¹H NMR (400 MHz, DMSO-d₆) δppm 1.04 (s, 0H) 1.51 (br. s., 1 H) 1.53-1.58 (m, 3 H) 1.67 (br. s., 2H) 2.10-2.25 (m, 1 H) 2.34-2.43 (m, 1 H) 3.07 (s, 3 H) 3.28 (s, 2 H)3.44-3.53 (m, 1 H) 3.65-3.75 (m, 1 H) 3.89 (s, 3 H) 4.00-4.16 (m, 2 H)4.95 (s, 1 H) 5.09 (s, 2 H) 6.58-6.67 (m, 2 H) 6.78-6.85 (m, 1 H) 7.10(s, 2 H) 7.59-7.68 (m, 2 H) 7.69-7.74 (m, 1 H) 7.74-7.82 (m, 1 H) 8.26(s, 1 H) 11.60 (s, 1 H)

Step E:(2R)-N-hydroxy-4-[4-{4-[(6-methoxypyridin-3-yl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

HCl (1.0 N in water, 2.09 mL) was added to a solution of the(2R)-4-[4-{4-[(6-methoxypyridin-3-yl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(245 mg, 0.418 mmol) in IPA (5.0 mL) for 1 hour. The reaction mixturewas concentrated and the residue was triturated with IPA to afford awhite suspension at 50° C. for 30 minutes. A white solid was collectedby filtration. Yield 215 mg/95% LCMS MS ES-500.1. ¹H NMR (400 MHz,DMSO-d₆) δ ppm 1.54 (s, 3 H) 2.07-2.23 (m, 1 H) 2.33-2.43 (m, 1 H) 3.08(s, 3 H) 3.64-3.79 (m, 1 H) 3.83 (s, 3 H) 4.00-4.12 (m, 1 H) 5.09 (s, 3H) 6.57-6.67 (m, 2 H) 6.80-6.88 (m, 1 H) 7.05-7.12 (m, 2 H) 7.64-7.73(m, 3 H) 7.78 (s, 1 H) 8.26 (s, 1 H).

Example 60(2R)-4-[4-{4-[difluoro(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A 8-[1,3]-Dithian-2-ylidene-1,4-dioxa-spiro[4,5]decane

The title compound can be made following the procedure described in Eur.J. Org. Chem. 2008, 3479-34871, except that 4-dioxaspiro[4.5]decan-8-onewas used as the ketone substrate. The resulting product was purified viasilica gel chromatography (10% ethyl acetate 90% heptane to 100% ethylacetate over 45 minutes. Isolated (6000 mg, ˜100%).LCMS 259.2 ¹H NMR(400 MHz, CHLOROFORM-d) δ ppm 1.67 (s, 4 H) 2.12 (qq, 2 H) 2.57-2.63 (m,4 H) 2.83-2.89 (m, 4 H) 3.93-3.96 (m, 4 H)

Step B: 8-((4-bromophenoxy)difluoromethyl)-1,4-dioxaspiro[4.5-]decane

Trifluoromethanesulfonic acid (0.681 mL, 7.82 mmoles) was added dropwiseto a stirred solution of8-[1,3]dithian-2-ylidene-1,4-dioxa-spiro[4,5]decane (2000 mg, 7.740mmoles) in 25 mL of dichloromethane at −22° C. The solution was allowedto warm to room temperature and stirred for 30 minutes The blackreaction mixture was cooled to −720C and a solution of 4-bromo-phenol(2010 mg, 11.6 mmoles) and triethylamine (1.90 mL, 13.6 mmoles) in 25 mLof dichloromethane was added (solution turned red). The reaction wasallowed to stir for an hour at −72° C., before NEt3.3HF (6.31 mL, 38.7mmoles) was added. After 5 minutes a suspension of DBH(1,3-dibromo-5,5-dimethylhydanthoin) (11.1 g, 38.7 mmoles) in 25 mL's ofdichloromethane was added in portions over 30 minutes (solution turnedgreenish/black). The solution was stirred for an additional hour, thenwarmed to 0° C. and poured into a solution of 1 N NaOH. The organiclayer was separated, washed with water, dried over sodium sulfate,filtered and concentrated in vacuo. The crude material was purified viasilica gel chromatography and was eluted with 20% ethyl acetate 80%heptane to 100% ethyl acetate for 45 minutes. The isolated product wastaken on directly to the next step. (2.811 g, 24.9%).

Step C: 4-[(4-bromo-phenoxy)-difluoro-methyl]-cyclohexanone

4 N HCl (4.23 mL, 16.9 mmoles) was added to a solution of8-((4-bromophenoxy)difluoromethyl)-1,4-dioxaspiro[4.5]decane (1230 mg,3.387 mmoles) in acetone (11.3 mL, 0.3M) and was allowed to stirovernight at room temperature. The reaction mixture was concentratedonto silica gel and purified via chromatography (9:1 heptane:ethylacetate to 3:7 heptane:EtOAc over 40 minutes followed by 100% EtOAc for10 minutes) afforded the desired material (1081 mg, 97.13%). ¹H NMR (400MHz, METHANOL-d₄) δ ppm 1.27 (br. s., 2 H) 1.39-1.51 (m, 2 H) 1.96-2.10(m, 5 H) 3.32-3.38 (m, 0 H) 3.47-3.55 (m, 1 H) 7.05-7.13 (m, 2 H)7.45-7.53 (m, 2 H)

Step D: trans-4-[(4-bromophenoxy)(difluoro)methyl]cyclohexanol

To a stirred solution of4-[(4-bromo-phenoxy)-difluoro-methyl]-cyclohexanone (1050 mg, 3.290mmoles) in ethanol (16.4 mL, 0.2M) was added NaBH₄ (249 mg, 6.58 mmoles)0° C. The solution was stirred at 0° C. for 20 minutes and then warmedto room temperature for 20 minutes. The reaction was quenched with 1 NHCl to a pH of ˜7, and extracted three times with ethyl acetate. Theorganics where combined, dried over magnesium sulfate, filtered andconcentrated. Cis/trans isomers were then separated by chiralpurification. Isolated 260 mg of trans isomer (24%). ¹H NMR (400 MHz,METHANOL-d₄) δ ppm 1.39 (s, 2 H) 1.51-1.65 (m, 2 H) 1.83-1.96 (m, 2 H)2.01-2.21 (m, 2 H) 2.38-2.47 (m, 1 H) 7.03-7.14 (m, 2 H) 7.41-7.58 (m, 2H)

Step E:(2R)-4-[4-{4-[difluoro(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,T8, (240 mg, 0.495 mmoles), which may be produced as in Preparation 3,trans-4-[(4-bromophenoxy)(difluoro)methyl]cyclohexanol (159 mg, 0.495mmoles), potassium carbonate (274 mg, 1.98 mmoles), and dioxane (3 mL,0.2 M) were added to a 5 mL microwave vial followed by the addition ofwater and Pd EnCat™ (128 mg, 0.05 mmole, loading factor 0.39 mmol/g).The reaction mixture was irradiated at 120° C. for 45 minutes. The crudematerial was filtered through a thin film of celite and was rinsed withethyl acetate then the filtrate was concentrated in vacuo. The materialwas purified via silica gel chromatography (15% EtOAc 85% heptane to100% ethyl acetate over 45 minutes and then 5% MeOH 95% ethyl acetatefor an additional 5 minutes). Isolated 290 mg title compound (95.6%)LCMS ES-611.8

Step F:(2R)-4-[4-{4-[difluoro(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

To a stirred solution of(2R)-4-[4-{4-[difluoro(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(280 mg, 0.473 mM) in 2.3 mL of dichloromethane was added a solution of4 M HCl in dioxane (0.120 mL, 0.473 mM). The reaction mixture wasallowed to stir for 20 minutes before being treated with 0.5 mL of MeOH.Reaction was concentrated in vacuo and purified by reverse phase(Shimadzu) prep HPLC 35 mg, (14%). LCMS 529.1 ¹H NMR (400 MHz,METHANOL-d₄) δ ppm 1.30 (br. s., 2 H) 1.40-1.54 (m, 2 H) 1.64-1.74 (m, 3H) 1.99-2.14 (m, 4 H) 2.31-2.42 (m, 1 H) 2.51-2.67 (m, 1 H) 3.09 (s, 3H) 3.45-3.62 (m, 1 H) 3.87-4.02 (m, 1 H) 4.23-4.34 (m, 1 H) 6.70-6.75(m, 1 H) 6.78 (s, 1 H) 7.21-7.33 (m, 2 H) 7.65-7.74 (m, 3 H)

Example 61(2R)-N-hydroxy-4-[4-{4-[4-(hydroxymethyl)piperidin-1-yl]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

Step A) [1-(4-bromo-phenyl)-piperidin-4-yl]-methanol

A mixture of 1-bromo-4-iodo-benzene (2.5 g, 8.8 mmol),piperidine-4-yl-methanol (2.0 g, 17.7 mmol), potassium phosphate (3.8 g,17.7 mmol) and copper (I) iodide (3.8 g, 17.7 mmol) in N,N-dimethylethanolamine (8.4 mL) was heated to 55° C. for 48 hours. The mixture wasallowed to cool to ambient temperature, water was added and the mixturewas extracted with ether 2×. The combined organic extracts were washedwith water 3×. The organic extract was dried over magnesium sulfate,filtered and concentrated to a crude residue. The residue was dissolvedin methylene chloride and passed through a silica gel pad. The pad waseluted ethyl acetate/heptanes (3:7) to ethyl acetate/heptanes (6:4) andthe filtrate was concentrated in vacuo to afford[1-(4-bromo-phenyl)-piperidin-4-yl]-methanol as a white solid. (2.4 g)

Step B){1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-piperidin-4-yl}-methanol

[1-(4-Bromo-phenyl)-piperidin-4-yl]-methanol (380 mg, 1.41 mmol), wasdissolved in 1,4-dioxane (10 mL, degassed with nitrogen).Bis(pinacolato)diborane (428 mg, 1.69 mmol), potassium acetate (414 mg,4.22 mmol) and palladium dichloride dppf (115 mg, 0.141 mmol) were addedat ambient temperature. The resulting mixture was stirred at 90° C.overnight. A further portion of bis(pinacolato)diborane (358 mg, 1.41mmol) was added and the mixture was stirred at 90° C. overnight. Themixture was cooled to ambient temperature, filtered thought a pad ofcelite, rinsed with ethyl acetate and the filtrate was concentrated to acrude residue. The residue was absorbed onto silica gel and purified viaflash column chromatography (gradient: 100% heptanes to 2:8 ethylacetate/heptanes to 1:1 ethyl acetate/heptanes). The fractionscontaining desired product were combined and concentrated to afford{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-piperidin-4-yl}-methanol(399 mg)

Step C:(R)-4-{4-[4-(4-Hydroxymethyl-piperidin-1-yl)-phenyl]-2-oxo-2H-pyridin-1-yl}-2-methanesulfonyl-2-methyl-N-(tetrahydro-pyran-2-yloxy)-butyramide.

Water (1 mL, degassed with nitrogen) was added to a mixture of potassiumcarbonate (277 mg, 2.0 mmol),(R)-4-(4-iodo-2-oxo-2H-pyridin-1-yl)-2-methanesulfonyl-2-methyl-N-(tetrahydro-pyran-2-yloxy)-butyramide(200 mg, 0.4 mmol), which may be produced as in Preparation 2B, and{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-piperidin-4-yl}-methanol(153 mg, 0.48 mmol) in 1,4-dioxane (4 mL, degassed with nitrogen) atambient temperature. To this mixture was added Pd Encat (103 mg, 0.04mmol, 0.39 mmol/g load) and the mixture was heated to 80° C. overnight.The mixture was cooled to ambient temperature and filtered through a padof celite. The pad was rinsed with ethyl acetate and the filtrate wasconcentrated to a crude residue. The residue was purified via combiflashcompanion. The desired fractions were collected, combined andconcentrated in vacuo to afford(R)-4-{4-[4-(4-Hydroxymethyl-piperidin-1-yl)-phenyl]-2-oxo-2H-pyridin-1-yl}-2-methanesulfonyl-2-methyl-N-(tetrahydro-pyran-2-yloxy)-butyramide.(85.1 mg)

Step D:(R)-N-Hydroxy-4-{4-[4-(4-hydroxymethyl-piperidin-1-yl)-henyl]-2-oxo-2H-pyridin-1-yl}-2-methanesulfonyl-2-methyl-butyramide

(R)-4-{4-[4-(4-hydroxymethyl-piperidin-1-yl)-phenyl]-2-oxo-2H-pyridin-1-yl}-2-methanesulfonyl-2-methyl-N-(tetrahydro-pyran-2-yloxy)-butyramide(85.1 mg, 0.152 mmol) was dissolved in methylene chloride (5 mL) atambient temperature. To this solution was added 4M HCl in 1,4-dioxane(0.304 mL, 1.22 mmol) and methanol (1 ml). The resulting solution wasstirred at ambient temperature for 45 minutes. The solution wasconcentrated to a crude residue in vacuo. To the residue was added ethylacetate (10 ml) and the resulting slurry was stirred overnight atambient temperature. The slurry was filtered and washed with ethylacetate/heptanes (1:1). The solid was dried in vacuo to afford(R)-N-Hydroxy-4-{4-[4-(4-hydroxymethyl-piperidin-1-yl)-phenyl]-2-oxo-2H-pyridin-1-yl}-2-methanesulfonyl-2-methyl-butyramidehydrochloride as an off-white solid. (72.7 mg). LCMS: M+1 478.6. ¹H NMR(CD₃OD, 400 MHZ) dppm, 7.82 (2H, d), 7.79 (1H, d), 6.84 (1H, d),6.80-6.77 (1H, dd), 4.35-4.28 (1H, m), 4.00-3.93 (1H, m), 3.79-3.72 (4H,m), 3.55 (2H, d), 3.09 (3H, s), 2.64-2.56 (1H, m), 2.40-2.33 (1H, m),2.16-2.13 (2H, d), 2.00-1.92 (1H, m), 1.87-1.76 (2H, m), 1.70 (3H, s).

Example 62N-hydroxy-4-[4-{4-[(1E)-N-methoxyethanimidoyl]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

Step A:4-[4-(4-Acetylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

4-Acetylphenylboronic acid was converted to the title product followingthe general procedure outlined for(2R)-4-[4-(2-fluoro-4-methylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidein Example 13. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.58 (s, 3 H) 2.17 (ddd,J=12.83, 11.56, 5.07 Hz, 1 H) 2.40-2.49 (m, 1 H) 2.62 (s, 3 H) 3.11 (s,3 H) 3.77 (td, J=11.95, 4.78 Hz, 1 H) 4.13 (td, J=11.90, 5.07 Hz, 1 H)6.70 (dd, J=7.22, 2.15 Hz, 1 H) 6.79 (d, J=2.15 Hz, 1 H) 7.81 (d, J=7.03Hz, 1 H) 7.87 (d, J=8.39 Hz, 2 H) 8.04 (d, J=8.59 Hz, 2 H) 11.14 (br.s., 1 H).

Step B:N-Hydroxy-4-[4-{4-[(1E)-N-methoxyethanimidoyl]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

A suspension of4-[4-(4-acetylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide(105 mg, 0.258 mmol), O-methylhydroxylamine hydrochloride (86.2 mg, 1.03mmol) and sodium acetate (107 mg, 1.03 mmol) in ethanol (10 mL, 0.025M)was heated in an oil bath at 70° C. for 3 hours. The volatiles wereremoved by rotary evaporation. The remaining material was redissolved in1.5 mL DMSO and run on Shimadzu HPLC 30×100 mm reverse phase column. Thematerial was eluted with 20-35% acetonitrile in water with 0.1% ammoniumhydroxide modifier. The gradient was run for 8 min then held at 35% foran additional two minutes. The desired material eluted at about 30%acetonitrile. This solution was concentrated down by rotary evaporationyielding 90.7 mg (80.7%) of the title compound a white solid. LC/MS m/z436 (M+1). ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.57 (s, 3 H) 2.13-2.21 (m, 1H) 2.21 (s, 3 H) 2.39-2.48 (m, 1 H) 3.11 (s, 3 H) 3.70-3.81 (m, 1 H)3.94 (s, 3 H) 4.12 (td, J=11.90, 5.00 Hz, 1 H) 6.68 (dd, J=7.20, 1.83Hz, 1 H) 6.75 (d, J=1.95 Hz, 1 H) 7.71-7.82 (m, 5 H) 9.27 (br. s., 1 H)11.14 (br. s., 1 H)

Example 63N-Hydroxy-4-[4-{4-[3-(hydroxymethyl)isoxazol-5-yl]-3-methylphenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

Step A:5-(4-bromo-2-methylphenyl)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]isoxazole

To a flask containing a solution of 4-bromo-1-ethynyl-2-methylbenzene(875 mg, 4.49 mmol) (may be prepared according to the procedures inJournal of Chemical Research (2007), 12 728-732) in toluene (20 mL), wasadded 2-(2-nitroethoxy)tetrahydro-2H-pyran (1.34 g, 7.63 mmol), phenylisocyanate (1.82 g, 15.3 mmol), and triethylamine (1.50 mL, 10.8 mmol).The reaction was heated at 100° C. and stirred under nitrogen overnight.The reaction was cooled, quenched with methanol and filtered. Thefiltrate was evaporated in vacuo onto silica gel. Chromatography onsilica gel with a heptane-ethyl acetate gradient (0-35% ethyl acetate)eluted5-(4-bromo-2-methylphenyl)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]isoxazoleas an orange oil (581 mg, 36.8%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm1.57-1.71 (m, 4 H) 1.73-1.82 (m, 1 H) 1.82-1.91 (m, 1 H) 2.51 (s, 3 H)3.56-3.62 (m, 1 H) 3.89-3.96 (m, 1 H) 4.69 (d, J=12.88 Hz, 1 H)4.76-4.79 (m, 1 H) 4.86 (d, J=12.88 Hz, 1 H) 6.51 (s, 1 H) 7.42-7.46 (m,1 H) 7.48 (d, J=1.56 Hz, 1 H) 7.59 (d, J=8.20 Hz, 1 H).

Step B:5-[2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]isoxazole

5-(4-Bromo-2-methylphenyl)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]isoxazolewas converted to the title product following the procedure outlined for(+/−)-2-[(cis-4-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}cyclohexyl)oxy]tetrahydro-2H-pyranin Example 8, step D. The title compound was isolated as an orange oil,473 mg, 71.9%. ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.37 (s, 12 H)1.53-1.71 (m, 4 H) 1.73-1.82 (m, 1 H) 1.82-1.93 (m, 1 H) 2.54 (s, 3 H)3.55-3.63 (m, 1 H) 3.89-3.96 (m, 1 H) 4.69 (d, J=12.69 Hz, 1 H) 4.78 (t,J=3.51 Hz, 1 H) 4.86 (d, J=12.89 Hz, 1H) 6.55 (s, 1 H) 7.71-7.76 (m, 3H).

Step C: (2R)-4-[4-{4-[3-(hydroxymethyl)isoxazol-5-yl]-3-methylphenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

5-[2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]isoxazolewas converted to the title product following the procedure outlined for(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-{[cis-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methoxy}phenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamidein Example 8 step E. Isolated crude yellow foam, 488 mg, 110% (impure).LCMS 642 (M−1)

Step D: N-Hydroxy-4-[4-{4-[3-(hydroxymethyl)isoxazol-5-yl]-3-methylphenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide

(2R)-4-[4-{4-[3-(hydroxymethyl)isoxazol-5-yl]-3-methylphenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewas converted to title product following the procedure outlined for(2R)-N-hydroxy-4-[4-{4-[(cis-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamidein Example 8, step F. Isolated title compound as a tan solid, 256.5 mg,77.3%. 1H NMR (400 MHz, METHANOL-d₄) δ ppm 1.73 (s, 3 H) 2.37-2.45 (m, 1H) 2.60 (s, 3 H) 2.62-2.70 (m, 1 H) 3.11 (s, 3 H) 3.99-4.08 (m, 1 H)4.33-4.41 (m, 1 H) 4.72 (s, 2 H) 6.76 (s, 1 H) 6.96 (s, 2 H) 7.67 (dd,J=8.20, 1.56 Hz, 1 H) 7.72 (s, 1 H) 7.86 (d, J=8.20 Hz, 2 H). LCMS 476(M+1).

Example 64(2R)-N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(3-phenylazetidin-1-yl)pyridin-1(2H)-yl]butanamide

Step A:2(R)-2-Methyl-2-(methylsulfonyl)-4-[2-oxo-4-(3-phenylazetidin-1-yl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,T6, which may be produced as in Preparation 2B (309 mg, 0.620 mmol),3-phenylazetidine (185 mg, 1.39 mmol), potassium tert-butoxide (209 mg,1.86 mmol), and tris(dibenzylideneacetone)dipalladium(0) (26 mg, 0.025mmol) and +BINAP (23 mg, 0.037 mmol) were combined into a flask, placedunder vacuum and opened to nitrogen. Deoxygenated 1,2-dimethoxyethane(3.0 mL) and triethylamine (43 uL, 0.310 mmol) were added and thereaction was placed on vacuum and opened to nitrogen three times andthen heated at 80° C. under nitrogen overnight. The reaction was cooled,diluted with dichloromethane and methanol and evaporated in vacuo ontosilica gel. Chromatography on silica gel with a dichloromethane-methanolgradient (1%-20%) eluted(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(3-phenylazetidin-1-yl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamideas a yellow oil (192 mg, 61.7%).

LCMS 504 (M+1).

Step B:(2R)-N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(3-phenylazetidin-1-yl)pyridin-1(2H)-yl]butanamide

(2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(3-phenylazetidin-1-yl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamidewas converted to title product following the procedure outlined for(2R)-N-hydroxy-4-[4-{4-[(cis-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamidein Example 8, step F. Isolated title compound as a white solid, 55.0 mg,34.8%. ¹H NMR (400 MHz, METHANOL-d₄) δ ppm 1.67 (s, 3 H) 2.23-2.38 (m, 1H) 2.41-2.55 (m, 1 H) 3.10 (s, 3 H) 3.70-3.87 (m, 1 H) 3.95-4.05 (m, 3H) 4.07-4.21 (m, 1 H) 4.35-4.48 (m, 2 H) 5.28-5.34 (m, 1 H) 5.82-5.93(m, 1 H) 7.21-7.30 (m, 1 H) 7.33-7.38 (m, 3 H) 7.38-7.46 (m, 2 H). LCMS420 (M+1)

Example 65(2R)-N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(phenylethynyl)pyridin-1(2H)-yl]butanamide

Step A:(2R)-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-(phenylethynyl)pyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,T6, which may be produced as in Preparation 2B (200 mg, 0.401 mmol) wasdissolved in tetrahydrofuran (5 mL) and diisopropylethylamine (2 ml) atroom temperature. The solution was degassed with nitrogen over a 5minute period. Palladium tetrakis (23.3 mg, 0.020 mmol), copper iodide(7.80 mg, 0.040 mmol), and phenylacetylene (49.1 mg, 0.481 mmol) wereadded to the reaction. The reaction was allowed to stir at roomtemperature for 3 hours under a nitrogen atmosphere. The reaction wasdiluted with ethyl acetate (200 ml) and was extracted with a saturatedaqueous solution of ammonium chloride (100 ml). The organic layer waswashed with brine, dried over sodium sulfate, and evaporated in vacuo.The crude material was purified via silica chromatography, using50%-100% [ethyl acetate/hexanes] as the gradient elution solvent. Thetarget fractions were combined and concentrated in vacuo to afford aviscous, colorless oil that crystallized upon standing. Yield 107 mg,57%. MS (APCI) m/z 471.5 (M−H) ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm1.57-1.65 (m, 2 H) 1.69 (d, J=1.95 Hz, 3 H) 1.71-1.98 (m, 4 H) 2.30-2.42(m, 1 H) 2.43-2.55 (m, 1 H) 3.19 (d, J=3.32 Hz, 3 H) 3.56-3.69 (m, 1 H)3.97-4.06 (m, 1 H) 4.13-4.25 (m, 1 H) 4.26-4.36 (m, 1 H) 5.16 (dt,J=16.00, 2.63 Hz, 1 H) 6.34 (dd, J=7.02, 1.76 Hz, 1 H) 6.75 (s, 1 H)7.29 (d, J=7.02 Hz, 1 H) 7.34-7.40 (m, 3 H) 7.52 (dd, J=7.32, 1.85 Hz, 2H) 12.00 (br. s., 1 H)

Step B:(R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-(phenylethynyl)pyridin-1(2H)-yl)butanamide

A solution of 1.0 M aqueous HCl (10 ml) was added slowly to a solutionof(2R)-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-(phenylethynyl)pyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(107 mg, 0.226 mmol) in 1,4-dioxane (20 mL) at room temperature. Thereaction mixture was allowed to stir at room temperature overnight.After 18 hours the reaction was concentrated to low volume thenredissolved in methanol (20 ml) and concentrated in vacuo to afford alight-yellow solid. Yield 71 mg, 81%. MS (APCI) m/z 389.4 (M+H), ¹H NMR(400 MHz, DMSO-d₆) δ ppm 1.46 (none, 3 H) 1.53 (s, 3 H) 2.03-2.17 (m, 1H) 2.33-2.45 (m, 1 H) 3.07 (s, 3 H) 3.71 (td, J=11.90, 4.88 Hz, 1 H)3.96-4.14 (m, 1 H) 6.35 (dd, J=6.93, 1.85 Hz, 1 H) 6.56 (d, J=1.76 Hz, 1H) 7.36-7.48 (m, 3 H) 7.51-7.61 (m, 2 H) 7.69 (d, J=7.02 Hz, 1 H) 11.05(br. s., 1 H)

Example 66

4-[4-(3-Cyclohexylpropoxy)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Step A: ethyl4-(4-hydroxy-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

Ethyl4-[4-(benzyloxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoate(2.4 g, 5.9 mmol) which may be prepared by the same method disclosed inExample 51, step A, was dissolved in ethanol (100 ml) and cooled with adry ice/acetone bath. To the cooled solution was added Pearlman'scatalyst (2.0 g) and cyclohexene (9.0 ml, 88.4 mmol) then heated to 85°C. for 3 hours. The reaction mixture was cooled to RT and filteredthrough celite (approx 2 inches) to remove catalyst. The celite waswashed with an additional 100 ml of ethanol. The filtrate was thenconcentrated under reduced pressure and the residue was dried undervacuum to afford a light gray solid. (1.75 g, 94%). MS (LC/MS) m/z 318.1(M+1) ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.22 (t, J=7.02 Hz, 3 H) 1.56 (s,3 H) 2.02-2.26 (m, 1 H) 2.33-2.48 (m, 1 H) 3.14 (s, 3 H) 3.67-3.84 (m,1H) 3.84-4.02 (m, 1H) 4.13 (dd, J=7.02, 4.49 Hz, 2H) 5.55 (d, J=2.54 Hz,1H) 5.85 (dd, J=7.42, 2.54 Hz, 1H) 7.48 (d, J=7.42 Hz, 1H)

Step B:4-[4-(3-cyclohexylpropoxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoicacid

Ethyl4-(4-hydroxy-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate(285 mg, 0.898 mmol) was weighed into a 20 ml septa cap vial with THF(10 ml) added. To this was added 3-cyclohexyl-1-propanol (0.191 ml, 1.26mmol), followed by triphenylphosphine (330 mg, 1.21 mmol). The reactionmixture was stirred at RT for 20 minutes and then DIAD (0.248 ml, 1.26mmol) was added. The reaction mixture was stirred for 72 hours at RT,was then diluted with ethyl acetate (100 ml) and washed with saturatedsodium bicarbonate (50 ml). The product was re-extracted with ethylacetate (100 ml). The organic phases were combined, dried over sodiumsulfate, filtered and concentrated in vacuo. The residue was dissolvedin dioxane (6 ml) and ethanol (6 ml). To this was added a 2.0M aqueoussolution of LiOH (2.6 ml, 5.3 mmol). The reaction mixture was stirred atRT overnight, then was diluted with 30 ml of water and washed with ethylacetate (2×50 ml) to remove any TPPO. The aqueous phase was adjusted topH-2 with 1N HCl (10 ml) and the product was extracted with ethylacetate (3×50 ml). The organic phases were combined, dried over sodiumsulfate, filtered and concentrated to provide the title compound as awhite solid (190 mg, 51%). MS (LC/MS) m/z 414.1 (M+1) ¹H NMR (400 MHz,METHANOL-d₄) δ ppm 0.81-1.08 (m, 2 H) 1.16-1.44 (m, 6 H) 1.72 (s, 9 H)2.01 (s, 1 H) 2.29-2.47 (m, 1 H) 2.48-2.68 (m, 1 H) 3.18 (s, 3 H) 4.04(s, 2 H) 4.07-4.17 (m, 1 H) 4.22-4.37 (m, 1 H) 5.97-6.12 (m, 1 H)6.25-6.36 (m, 1 H) 7.57-7.73 (m, 1 H)

Step C:4-[4-(3-cyclohexylpropoxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

4-[4-(3-Cyclohexylpropoxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoicacid (190 mg, 0.451 mmol) and CDMT (95.6 mg, 0.539 mmol) were chargedinto a flask. The flask was flushed with nitrogen and 2-MeTHF (10 ml)was added, followed by NMM (64 uL, 0.581 mmol). The reaction mixture wasstirred at RT for 1 hour. O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (64mg, 0.539 mmol) was added to the reaction mixture and stirred for 16hours at RT. Water (25 ml) was added, the layers were separated and theaqueous layer was extracted with EtOAc (3×50 ml). The organic layerswere combined and dried over sodium sulfate, filtered and concentratedin vacuo. Crude material was purified by chromatography on silica gel(70% heptane:30% ethyl acetate to 100% ethyl acetate) to afford a whitesolid (220 mg, 79%). MS (LC/MS) m/z 511.1 (M−1) ¹H NMR (400 MHz,METHANOL-d₄) δ ppm 0.93 (t, J=7.02 Hz, 3 H) 1.12-1.42 (m, 9 H) 1.49-1.99(m, 10 H) 2.25-2.43 (m, 1 H) 2.45-2.64 (m, 1 H) 3.12 (d, J=5.07 Hz, 3 H)3.51-3.68 (m, 2 H) 3.82-4.03 (m, 4 H) 4.08-4.26 (m, 2 H) 5.03-5.14 (m, 1H) 5.94 (d, J=2.54 Hz, 1 H) 6.07-6.21 (m, 1 H) 7.45-7.60 (m, 1 H).

Step D:4-[4-(3-cyclohexylpropoxy)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

4-[4-(3-Cyclohexylpropoxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(220 mg, 0.429 mmole) was dissolved in dioxane (4 ml), DCM (4 ml) andwater (2 ml). To this was added a 4.0M solution of HCl in dioxane (1.0ml, 4.29 mmole) and was stirred at RT for 1 hour. The reaction mixturewas concentrated in vacuo and azeoptroped with IPA (2×5 ml) to afford awhite solid (100 mg, 54.4%). MS (LC/MS) m/z 429.1 (M+1) ¹H NMR (400 MHz,METHANOL-d₄) δ ppm 0.83-1.06 (m, 3 H) 1.19-1.40 (m, 6 H) 1.41 (s, 2 H)1.64-1.90 (m, 4 H) 2.31-2.41 (m, 1 H) 2.61-2.79 (m, 1 H) 3.08 (s, 3 H)3.60 (s, 1 H) 3.63-3.71 (m, 1 H) 3.86-3.99 (m, 2 H) 4.04 (s, 1 H) 4.11(d, J=8.00 Hz, 3 H) 4.25-4.41 (m, 1 H) 6.29 (s, 1 H) 6.53-6.68 (m, 1 H)7.83-7.93 (m, 1 H)

Example 67(2R)-N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-1′-pyrimidin-2-yl-1′,2′,3′,6′-tetrahydro-4,4′-bipyridin-1(2H)-yl)butanamide

Step A:2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridin-1(2H)-yl]pyrimidine

To a flask containing 1-pyrimidin-2-yl-1,2,3,6-tetrahydropyridin-4-yltrifluoromethanesulfonate (300 mg, 0.970 mmol) (may be preparedaccording to the procedures in PCT Int Appl 2006124897),bis(pinacolato)diboron (296 mg, 1.16 mmol), potassium acetate (288 mg,2.91 mmol), 1,1′-bis-(diphenylphosphino)ferrocene (16 mg, 0.029 mmol)and [1,1′-bis-(diphenylphosphino)ferrocene]-dichloropalladium(II)dichloromethane complex (71 mg, 0.097 mmol) was added deoxygenated1,4-dioxane (5.0 ml). The reaction was placed under vacuum and opened tonitrogen three times and then heated at 80° C. under nitrogen overnight.The reaction was cooled and purified directly by chromatography onsilica gel with 6:1 heptane-ethyl acetate to give2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridin-1(2H)-yl]pyrimidineas a yellow solid (210 mg, 75.4%). ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm1.29 (s, 12 H) 2.25-2.44 (m, 2 H) 3.89 (t, J=5.66 Hz, 2 H) 4.24-4.29 (m,1 H) 6.42-6.54 (m, 1 H) 6.58-6.69 (m, 1 H) 8.21-8.40 (m, 2 H). LCMS:288.4 M+1.

Step B:(2R)-2-methyl-2-(methylsulfonyl)-4-(2-oxo-1′-pyrimidin-2-yl-1′,2′,3′,6′-tetrahydro-4,4′-bipyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide,T6, which may be produced as in Preparation 2B (310 mg, 0.622 mmol),2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridin-1(2H)-yl]pyrimidine(210 mg, 0.731 mmol), potassium carbonate (430 mg, 3.11 mmol), and PdEnCat™ (159 mg, 0.062 mmol) were combined into a flask, placed undervacuum and opened to nitrogen. Deoxygenated 1,4-dioxane (4.0 mL) andwater (1.0 mL) were added and the reaction was placed on vacuum andopened to nitrogen three times and then heated at 80° C. under nitrogenfor 16 hours. The reaction mixture was cooled, diluted with ethylacetate and filtered through celite. The filtrate was concentrated ontosilica gel in vacuo. Chromatography on silica gel with adichloromethane-methanol gradient (1%-20%) afforded(2R)-2-methyl-2-(methylsulfonyl)-4-(2-oxo-1′-pyrimidin-2-yl-1′,2′,3′,6′-tetrahydro-4,4′-bipyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideas a brown oil (140 mg, 42.5%). LCMS 530 (M−1).

Step C:(2R)-N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-1′-pyrimidin-2-yl-1′,2′,3′,6′-tetrahydro-4,4′-bipyridin-1(2H)-yl)butanamide

(2R)-2-methyl-2-(methylsulfonyl)-4-(2-oxo-1′-pyrimidin-2-yl-1′,2′,3′,6′-tetrahydro-4,4′-bipyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide(140 mg, 0.253 mmol) was converted to title product following theprocedure outlined for(2R)-N-hydroxy-4-[4-{4-[(cis-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamidein Example 8, step F. Isolated title compound as an off white solid(94.8 mg 80.5%). ¹H NMR (400 MHz, METHANOL-d₄) δ ppm 1.70 (s, 3 H)2.29-2.42 (m, 1 H) 2.55-2.67 (m, 1 H) 2.68-2.78 (m, 2 H) 3.10 (s, 3 H)3.93-4.04 (m, 1 H) 4.17 (t, J=5.76 Hz, 2 H) 4.26-4.37 (m, 1 H) 4.49-4.55(m, 2 H) 6.62 (br. s., 1 H) 6.67 (s, 1 H) 6.74-6.85 (m, 1 H) 7.07 (t,J=5.37 Hz, 1 H) 7.75 (d, J=7.81 Hz, 1 H) 8.67 (d, J=5.46 Hz, 2 H). LCMS:448 (M+1).

Examples 68-A to 68-U

The following compounds can be made following the procedures describedherein. Products are typically derived from a Suzuki-Miyaura crosscoupling with optional deprotection of a terminal hydroxamic acidprotecting group. Methods used to describe the synthesis of theprecursors or coupling partners such as boronic acids or esters areknown to those skilled in the art.

TABLE 3 Example Retention Mass number IUPACNAME Time ion¹ Purity NMRE68-A (2R)-N-hydroxy-2- 415 100 1H NMR (400 MHz, METHANOL-d4) methyl-2-d ppm 1.74 (s, 3 H) 2.31-2.55 (m, 1 (methylsulfonyl)-4- H) 2.64-2.83 (m,1 H) 3.10 (s, 3 H) [4-(2-naphthyl)-2- 3.96-4.24 (m, 1 H) 4.30-4.59 (m, 1oxopyridin-1(2H)- H) 7.17 (d, J = 1.95 Hz, 1 H) yl]butanamide 7.23-7.29(m, 1 H) 7.52-7.63 (m, 2 H) 7.78-7.86 (m, 1 H) 7.89-7.96 (m, 1 H E68-B(2R)-4-[4-(4-chloro- 415 (m − 1) ¹H NMR (400 MHz, DMSO-d₆) d ppm3-fluorophenyl)-2- 1.57 (s, 3 H) 2.11-2.21 (m, 1 H)oxopyridin-1(2H)-yl]- 2.38-2.48 (m, 1 H) 3.11 (s, 3 H) 3.76 (td,N-hydroxy-2-methyl- J = 11.95, 4.78 Hz, 1 H) 4.11 (td,2-(methylsulfonyl)butanamide J = 11.81, 5.07 Hz, 1 H) 6.69 (dd, J =7.12, 2.05 Hz, 1 H) 6.80 (d, J = 1.95 Hz, 1 H) 7.60-7.65 (m, 1 H)7.67-7. E68-C (2R)-4-[4-(3,4- 433 100 ¹H NMR (400 MHz, DMSO-d₆) d ppmdichlorophenyl)-2- 1.57 (s, 3 H) 2.16 (td, J = 12.20, 5.07 Hz,oxopyridin-1(2H)-yl]- 1 H) 2.38-2.48 (m, 1 H) 3.10 (s,N-hydroxy-2-methyl- 3 H) 3.76 (td, J = 11.90, 4.88 Hz, 1 H)2-(methylsulfonyl)butanamide 4.12 (td, J = 11.85, 4.98 Hz, 1 H) 6.70(dd, J = 7.12, 2.05 Hz, 1 H) 6.80 (d, J = 1.95 Hz, 1 H) 7.74 (d, J =0.98 Hz E68-D (2R)-N-hydroxy-2- 0.48 448 100 1H NMR (400 MHz, DMSO-d6) dmethyl-2- ppm 1.58 (s, 3 H) 2.18 (td, J = 12.05, (methylsulfonyl)-4-4.98 Hz, 1 H) 2.40-2.48 (m, 1 H) {2-oxo-4-[4-(1,3- 3.11 (s, 3 H) 3.77(td, J = 12.15, 5.37 Hz, thiazol-2- 1 H) 4.08-4.19 (m, 1 H)yl)phenyl]pyridin- 6.72 (dd, J = 7.22, 2.15 Hz, 1 H) 6.79 (d,1(2H)-yl}butanamide J = 2.15 Hz, 1 H) 7.80 (d, J = 7.22 Hz, 1 H) 7.84E68-E (2R)-4-[4-(2-chloro- 0.55 413 100 ¹H NMR (400 MHz, DMSO-d₆) d ppm3-methylphenyl)-2- 1.55 (s, 3 H) 2.15 (td, J = 12.20, 5.07 Hz,oxopyridin-1(2H)-yl]- 1 H) 2.37 (s, 3 H) 2.38-2.45 (m,N-hydroxy-2-methyl- 1 H) 3.08 (s, 3 H) 3.74 (td, J = 12.00,2-(methylsulfonyl)butanamide 4.68 Hz, 1 H) 4.10 (td, J = 11.90, 5.07 Hz,1 H) 6.30 (dd, J = 7.02, 1.95 Hz, 1 H) 6.35 (d, J = 1.76 Hz, 1 H) 7.21E68-F (2R)-N-hydroxy-4-[4- 0.46 432 100 1H NMR (400 MHz, DMSO-d6) d(4-isoxazol-3- ppm 1.58 (s, 3 H) 2.11-2.23 (m, 1 ylphenyl)-2- H)2.38-2.46 (m, 1 H) 3.11 (s, 3 H) oxopyridin-1(2H)-yl]- 3.71-3.82 (m, 1H) 4.06-4.21 (m, 1 2-methyl-2- H) 6.72 (dd, J = 7.02, 2.15 Hz, 1 H)(methylsulfonyl)butanamide 6.80 (d, J = 2.15 Hz, 1 H) 7.24 (d, J = 1.76Hz, 1 H) 7.79 (d, J = 7.03 Hz, 1 H) 7.89 E68-G (2R)-N-hydroxy-2- 0.47421 94 ¹H NMR (400 MHz, DMSO-d₆) d ppm methyl-2- 1.07 (t, J = 7.22 Hz, 3H) 1.55 (s, 3 H) (methylsulfonyl)-4- 2.09-2.21 (m, 1 H) 2.36-2.45 (m, 1[2-oxo-4-(4- H) 3.05 (q, 2 H) 3.08 (s, 3 H) propionylphenyl)pyridin-3.74 (td, J = 12.10, 4.49 Hz, 1 H) 1(2H)-yl]butanamide 4.05-4.15 (m, 1H) 6.67 (dd, J = 7.02, 2.15 Hz, 1 H) 6.76 (d, J = 1.95 Hz, 1 H) 7.7E68-H (2R)-N-hydroxy-4-{4- 0.45 449 100 ¹H NMR (400 MHz, DMSO-d₆) d ppm[4-(cis-3-hydroxy-3- 1.31 (s, 3 H) 1.54 (s, 3 H)methylcyclobutyl)phenyl]- 2.02-2.19 (m, 3 H) 2.26-2.44 (m, 3 H)2-oxopyridin- 2.93-3.07 (m, 1 H) 3.08 (s, 3 H) 3.71 (td,1(2H)-yl}-2-methyl-2- J = 12.00, 4.68 Hz, 1 H)(methylsulfonyl)butanamide 4.03-4.14 (m, 1 H) 5.01 (s, 1 H) 6.61 (dd, J= 7.12, 2.05 Hz, 1 H) 6.66 (d, J = 2.15 Hz E68-I (2R)-N-hydroxy-2- 0.56433 100 ¹H NMR (400 MHz, DMSO-d₆) d ppm methyl-2- 1.58 (s, 3 H) 2.17(ddd, J = 12.83, (methylsulfonyl)-4- 11.56, 4.88 Hz, 1 H) 2.41-2.48 (m,1 {2-oxo-4-[4- H) 3.11 (s, 3 H) 3.78 (td, J = 11.90,(trifluoromethyl)phenyl]pyridin- 4.88 Hz, 1 H) 4.13 (td, J = 11.85, 4.98Hz, 1(2H)-yl}butanamide 1 H) 6.69 (dd, J = 7.12, 2.05 Hz, 1 H) 6.79 (d,J = 1.95 Hz, 1 H) 7.80-7.8 E68-J (2R)-N-hydroxy-2- 0.52 446 100 1H NMR(400 MHz, DMSO-d6) d methyl-4-{3-methyl- ppm 1.59 (s, 3 H) 2.01 (s, 3 H)2-oxo-4-[4-(2H-1,2,3- 2.20 (td, J = 12.29, 4.88 Hz, 1 H) 2.44 (td,triazol-2- J = 12.05, 4.59 Hz, 1 H) 3.12 (s, 3 H) yl)phenyl]pyridin-3.78 (td, J = 11.90, 4.68 Hz, 2 H) 1(2H)-yl}-2- 4.16 (td, J = 11.76,4.98 Hz, 1 H) 6.27 (d, (methylsulfonyl)butanamide J = 6.83 Hz, 1 H) 7.57(d, J = 8.78 Hz, 2 H) E68-K (2R)-4-(4-cyclohex- 369 ¹H NMR (400 MHz,METHANOL-d₄) 1-en-1-yl-2- d ppm 1.54 (s, 14 H) 1.60-1.66 (m,oxopyridin-1(2H)-yl)- 8 H) 1.69-1.77 (m, 9 H) N-hydroxy-2-methyl-2-2.09-2.15 (m, 8 H) 2.21-2.29 (m, 9 H) (methylsulfonyl)butanamide 2.36(dd, 4 H) 2.74 (dd, 4 H) 3.04 (s, 13 H) 4.11 (dd, 4 H) 4.21 (dd, 4 H)5.97-6.01 (m, 4 H) 7.51-7.54 (m, 4 H) 7.5 E68-L (2R)-4-(4-cyclohept- 383¹H NMR (400 MHz, CHLOROFORM- 1-en-1-yl-2- d) d ppm 1.50 (br. s., 1 H)oxopyridin-1(2H)-yl)- 1.51-1.55 (m, 1 H) 1.55-1.58 (m, 1 H)N-hydroxy-2-methyl-2- 1.67 (s, 3 H) 1.74-1.80 (m, 1 H)(methylsulfonyl)butanamide 1.78-1.81 (m, 1 H) 1.82-1.89 (m, 1 H)2.17-2.28 (m, 1 H) 2.26-2.31 (m, 1 H) 2.31-2.36 (m, 1 H) 2.38-2.42 (m, 1E68-M (2R)-N-hydroxy-4-[4-{4-[(3- 0.43 449 100 1H NMR (400 MHz,METHANOL-d4) hydroxycyclobutyl)methyl]phenyl}- d ppm 1.19 (t, 2 H)1.55-1.70 (m, 2 2-oxopyridin-1(2H)-yl]- H) 1.72 (s, 3 H) 1.96-2.13 (m, 1H) 2-methyl-2- 2.33-2.46 (m, 3 H) 2.53-2.66 (m, 1(methylsulfonyl)butanamide H) 2.73-2.84 (m, 2 H) 3.13 (s, 3 H) 3.56-3.68(m, 1 H) 3.88-3.99 (m, 1 H) 3.99-4.11 (m, 1 H) 4.23-4. E68-N(2R)-N-hydroxy-4-[4- 0.45 459 100 1H NMR (400 MHz, DMSO-d6) d{6-[(1S)-1- ppm 1.34-1.52 (m, 3 H) 1.60 (s, 3 hydroxyethyl]-2- H)2.13-2.30 (m, 1 H) naphthyl}-2- 2.38-2.49 (m, 1 H) 3.13 (s, 3 H)3.69-3.91 (m, oxopyridin-1(2H)-yl]- 1 H) 4.04-4.24 (m, 1 H) 2-methyl-2-4.85-5.02 (m, 1 H) 5.34 (d, J = 4.10 Hz, 1 H) (methylsulfonyl)butanamide6.81-6.85 (m, 1 H) 6.87 (d, J = 1.95 Hz, 1 H E68-O N-hydroxy-4-[4-(6-0.36 435 100 ¹H NMR (400 MHz, DMSO-d₆) hydroxy-5,6,7,8- ppm 1.54 (s, 3H) 1.59-1.69 (m, 2 tetrahydronaphthalen- H) 1.81-1.98 (m, 1 H)2-yl)-2-oxopyridin- 2.03-2.23 (m, 1 H) 2.28-2.40 (m, 2 H)1(2H)-yl]-2-methyl-2- 2.61-2.79 (m, 2 H) 2.82-2.97 (m, 2 H)(methylsulfonyl)butanamide 3.08 (s, 3 H) 3.58-3.79 (m, 1 H) 4.01-4.17(m, 1 H) 4.74-4.82 (m, 1 H) 6.52- E68-P (2R)-N-hydroxy-2- 0.61 447 1001H NMR (400 MHz, DMSO-d6) d methyl-2- ppm 1.57 (s, 3 H) 2.09-2.26 (m, 2(methylsulfonyl)-4- H) 2.38-2.48 (m, 1 H) 3.11 (s, 3 H)[2-oxo-4-(5-phenyl- 3.64-3.83 (m, 1 H) 4.05-4.17 (m, 12-thienyl)pyridin- H) 6.66 (s, 1 H) 6.67-6.71 (m, 1 H)1(2H)-yl]butanamide 7.31-7.42 (m, 1 H) 7.46 (s, 2 H) 7.62 (d, J = 3.90Hz, 1 H) 7.70-7.76 (m, E68-Q N-hydroxy-4-{4-[4- 0.29 409 100 ¹H NMR (400MHz, DMSO-d₆) d ppm (1-hydroxyethyl)phenyl]- 1.29 (s, 3 H) 1.47 (s, 3 H)2-oxopyridin- 2.08-2.21 (m, 1 H) 2.24-2.37 (m, 1 H) 3.02 (s,1(2H)-yl}-2-methyl-2- 3 H) 3.64-3.73 (m, 1 H) (methylsulfonyl)butanamide4.07-4.17 (m, 1 H) 4.66-4.76 (m, 1 H) 5.19 (br. s., 1 H) 6.53-6.62 (m, 2H) 7.34-7.43 (m, 2 H) 7.56-7.66 (m, 3 H) E68-R N-hydroxy-2-methyl- 0.51418 100 1H NMR (400 MHz, METHANOL-d4) 4-[4-(1-methyl-1H- d ppm 1.74 (s,3 H) 2.36-2.50 (m, 1 indol-2-yl)-2- H) 2.68 (s, 1 H) 3.14 (s, 3 H) 3.86(s, oxopyridin-1(2H)-yl]-2- 3 H) 3.90-4.14 (m, 1 H)(methylsulfonyl)butanamide 4.22-4.44 (m, 1 H) 6.65-6.76 (m, 2 H) 6.80(s, 1 H) 7.03-7.17 (m, 1 H) 7.23-7.35 (m, 1 H) 7.46 (d, J = 8.39 Hz, 1 HE68-S 4-[4-(2- 401 1H NMR (400 MHz, METHANOL-d4) cyclopentylethoxy)- dppm 1.09-1.33 (m, 2 H) 2-oxopyridin-1(2H)- 1.49-1.64 (m, 2 H) 1.62-1.75(m, 5 H) yl]-N-hydroxy-2- 1.75-1.92 (m, 4 H) 1.91-2.07 (m, 1 methyl-2-H) 2.25-2.42 (m, 1 H) (methylsulfonyl)butanamide 2.45-2.62 (m, 1 H) 3.12(s, 3 H) 3.76-3.95 (m, 1 H) 4.04 (t, J = 6.54 Hz, 2 H) 4.13-4.29 E68-TN-hydroxy-2-methyl- 409 1H NMR (400 MHz, METHANOL-d4)2-(methylsulfonyl)- d ppm 1.69 (s, 3 H) 2.24-2.41 (m, 1 4-[2-oxo-4-(2-H) 2.61-2.76 (m, 1 H) 3.07 (s, 3 H) phenylethoxy)pyridin- 3.13 (t, J =6.63 Hz, 2 H) 1(2H)-yl]butanamide 3.87-3.99 (m, 1 H) 4.04 (s, 1 H)4.26-4.41 (m, 2 H) 6.28 (d, J = 2.73 Hz, 1 H) 6.51-6.63 (m, 1 H)7.16-7.27 (m, 1 H) 7 E68-U 4-[4-(4- 0.31 407 100 ¹H NMR (400 MHz,DMSO-d₆) d ppm acetylphenyl)-2- 1.58 (s, 3 H) 2.17 (ddd, J = 12.83,oxopyridin-1(2H)-yl]- 11.56, 5.07 Hz, 1 H) 2.40-2.49 (m, 1N-hydroxy-2-methyl- H) 2.62 (s, 3 H) 3.11 (s, 3 H) 3.77 (td,2-(methylsulfonyl)butanamide J = 11.95, 4.78 Hz, 1 H) 4.13 (td, J =11.90, 5.07 Hz, 1 H) 6.70 (dd, J = 7.22, 2.15 Hz, 1 H) 6.79 (d, J = 2.15Hz, 1 Foot note ¹Mass Spec.- See Method A as described in Table 5 infra.

Biological Examples

In order to assess the compounds biological activity, selected in-vitroassays were conducted on selected compounds. One of the assays measuredthe compounds ability to disrupt the synthesis of lipopolysaccharide,LPS, which is a component of the outer membrane of Gram-negativebacteria. Disruption of this synthesis is lethal to the bacteria. Theassay determined the compound's ability to inhibit LpxC, which is thefirst enzyme in the biosynthetic pathway for LPS (measured as IC₅₀).Additionally, MICs (minimal inhibitory concentrations) were determinedfor several bacteria. The specific protocols are described below:

A) IC₅₀ Assay, LpxC Enzyme from P. Aeruqinosa (Labeled as PA LpxC EnzymeIC₅₀):

IC₅₀ determination in the LpxC enzyme assay was carried out in a similarmanner to that described by Malikzay et al in the 2006 Poster, ScreeningLpxC (UDP-3-O—(R-3-hydroxymyristoyl)-GlcNAc deacetylase) using BioTroveRapidFire HTS Mass Spectrometry (aNew Lead Discovery and bInflammationand Infectious Disease, cStructural Chemistry, Schering-Plough ResearchInstitute, Kenilworth, N.J. 07033, (BioTrove, Inc. 12 Gill St., Suite4000, Woburn, Mass. 01801). Briefly, Pseudomonas aeruginosa LpxC enzyme(0.1 nM) purified from E. coli-overexpressing bacteria was incubated at25° C. in a final volume of 50 ul containing 0.5 uMUDP-3-O—(R-3-hydroxydecanoyl)-N-acetylglucosamine, 1 mg/mL BSA, and 50mM sodium phosphate buffer, pH 8.0 in the presence and absence ofinhibitor compound. At the end of 1 hour, 5 ul of 1N HCl was added tostop the enzyme reaction; the plates were centrifuged, and thenprocessed with the BioTrove Rapidfire HTMS Mass Spectrometry System. Ano-enzyme control was used in calculating the IC₅₀ values from thepercent conversion values.

B) MIC Determinations:

The in vitro antibacterial activity of compounds described in theExamples was evaluated by minimum inhibitory concentration (MIC) testingaccording to Clinical and Laboratory Standards Institute (CLSI, formerlyNCCLS) guidelines. See: Clinical and Laboratory Standards Institute.Methods for Dilution Antimicrobial Susceptibility Tests for Bacteriathat Grow Aerobically; Approved Standard-Seventh Edition. CLSI documentM7-A7 [ISBN 1-56238-587-9]. Clinical and Laboratory Standards Institute,940 West Valley Road, Suite 1400, Wayne, Pa. 19087-1898 USA, 2006; alsoClinical and Laboratory Standards Institute. Performance Standards forAntimicrobial Susceptibility Testing; Eighteenth InformationalSupplement. CLSI document M100-S18 [ISBN1-56238-653-0].Clinical andLaboratory Standards Institute.

The following bacterial strains were used in these MIC determinations:

1) Pseudomonas aeruginosa UI-18: Wild-type, labeled as PA-7 in Tables 4,and 5;

2) Acinetobacter baumanii/haemolyticus: Multidrug-resistant clinicalisolate labeled as AB-3167 in Tables 4 and 5;

3) Escherichia coli EC-1: VOGEL, mouse virulent labeled as EC-1 inTables 4 and 5;

4) Klebsiella pneumoniae: Ciprofloxacin-resistant isolate, expressesextended-spectrum beta-lactamases (ESBL), clinical isolate, labeled asKP-3700 in Tables 4, and 5.

Table 4 below shows the results that were obtained with the finalproducts described in Examples 1-69U. If a particular table is leftblank, then the data is not available at the current time.

Column 1 corresponds to the Example number, column 2 provides the IUPACname, column 3 provides the results from the LpxC enzyme assay describedabove, and columns 4-7 provide the MIC data as described above.

TABLE 4 Example Name-IUPAC PA:IC50 AB-3167 EC-1 KP-3700 PA-7  1(2R)-N-hydroxy-2-methyl-2- 0.000184 >64.0 0.5 2 2(methylsulfonyl)-4-{2-oxo-4-[4-(1H-pyrazol-1-yl)phenyl]pyridin-1(2H)-yl}butanamide  2 (2R)-N-hydroxy-2-methyl-2-0.000414 64 0.5 1 2 (methylsulfonyl)-4-{2-oxo-4-[(E)-2-phenylvinyl]pyridin-1(2H)-yl}butanamide  3 (2R)-N-hydroxy-2-methyl-2-0.000037 64 1 2 4 (methylsulfonyl)-4-[2-oxo-4-(2-phenylethyl)pyridin-1(2H)-yl]butanamide  44-[4-{4-[3-(4,4-difluoropiperidin-1- <0.00100 >64.0 1 2 4yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide  5(2R)-N-hydroxy-4-{4-[4-(cis-3- 0.000083 >64.0 4 8 2 hydroxycyclobutyl)phenyl]-2-oxopyridin- 1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide  6N-hydroxy-4-{4-[4-(3-hydroxycyclobutyl)phenyl]- 0.000272 >64.0 4 16 42-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl) butanamide  7(2R)-N-hydroxy-4-[4-{4-[(4- 0.00022 64 1 >64.0 2hydroxycyclohexyl)oxy]phenyl}-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl) butanamide  8 (2R)-N-hydroxy-4-[4-{4-[(cis-4-0.000187 >64.0 0.5 2 1 hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide  9(2R)-N-hydroxy-4-[4-{4-[(trans-4- 0.000122 32 0.25 2 1hydroxycyclohexyl)methoxy]phenyl}-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 10 (2R)-4-[4-{2-fluoro-4-[(trans-4-0.000154 >64.0 0.25 2 1 hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide10-A (2R)-N-hydroxy-4-[4-{4-[(4-hydroxy-4- 0.000201 >64.0 0.25 2 1methylcyclohexyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 10-B(2R)-N-hydroxy-4-[4-{4-[(3-hydroxy-3- 0.000106 >64.0 0.5 4 1methylcyclobutyl) methoxy]phenyl}-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 10-C (2R)-4-{4-[4-(3-cyanopropoxy)phenyl]-2-0.0000118 >64.0 0.5 2 1 oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 10-D (2R)-N-hydroxy-4-[4-(4-{[3-0.0000755 >64.0 0.25 2 1 (hydroxymethyl)cyclobutyl]methoxy}phenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 10-EN-hydroxy-4-[4-{4-[(4-hydroxy-4- >64.0 0.5 8 2methylpentyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 10-FN-hydroxy-4-[4-(4-{[3- 64 0.5 4 2(hydroxymethyl)cyclobutyl]oxy}phenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 10-G(2R)-N-hydroxy-4-[4-{4-[(4-hydroxy-4- 0.000376 64 0.5 4 2methylcyclohexyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 10-H(2R)-N-hydroxy-4-[4-(4-{[3-(1-hydroxy-1- 0.0000443 >64.0 1 8 2methylethyl)cyclobutyl]oxy}phenyl)-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 10-I (2R)-4-[4-{3-fluoro-4-[(4-hydroxy-4-0.000305 >64.0 0.5 8 2 methylcyclohexyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 10-JN-hydroxy-4-{4-[4-(2-hydroxy-2- >64.0 4 16 8methylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 10-K(2R)-4-[4-{4-[(3,4-dihydroxy-4- >0.100 >64.0 8 64 8methylpentyl)oxy]phenyl}-2-oxopyridin- 1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 10-L (2R)-4-[4-{2-fluoro-4-[(cis-4-0.0000508 >64.0 0.25 2 1 hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 11(2R)-N-hydroxy-2-methyl-2- 0.000264 64 8 8 1(methylsulfonyl)-4-(2-oxo-4-phenylpyridin- 1(2H)-yl)butanamide 12(2R)-4-[4-(2-fluoro-4-hydroxy-3- >64.0 16 32 16methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 13(2R)-4-[4-(2-fluoro-4-methylphenyl)-2- 0.0000746 >64.0 0.5 1 0.5oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 14(2R)-4-[4-(2,3-difluorophenyl)-2-oxopyridin- 0.0000255 >64.0 0.5 1 0.51(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 15(2R)-4-[4-(4-chlorophenyl)-2-oxopyridin- 0.0000402 >64.0 0.5 1 0.51(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 16(2R)-N-hydroxy-2-methyl-4-[4-(4- 0.0000673 >64.0 0.5 1 0.5methylphenyl)-2-oxopyridin-1(2H)-yl]-2- (methylsulfonyl)butanamide 17(2R)-N-hydroxy-4-[4-(4-methoxyphenyl)-2- 0.0000186 >64.0 0.5 1 0.5oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 18(2R)-4-[4-(2,3-dihydro-1,4-benzodioxin-6- 0.0003 >64.0 >64.0 2 1yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 19(2R)-N-hydroxy-2-methyl-4-[4-(2-methyl-1H- 0.000169 >64.0 1 4 2indol-5-yl)-2-oxopyridin-1(2H)-yl]-2- (methylsulfonyl)butanamide 20(2R)-4-[4-(4-chloro-2-fluorophenyl)-2- 0.000132 >64.0 0.25 0.5 0.25oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 21(2R)-4-[4-(2-fluoro-4-methoxyphenyl)-2- 0.000085 32 0.125 0.25 0.25oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 22(2R)-N-hydroxy-2-methyl-4-{4-[4-(2- 0.000432 >64.0 2 8 4methylpyrimidin-4-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 23 (2R)-N-hydroxy-2-methyl-2-0.000393 >64.0 2 64 2 (methylsulfonyl)-4-[2-oxo-4-(2,3,6-trifluorophenyl)pyridin-1(2H)-yl]butanamide 24(2R)-N-hydroxy-2-methyl-4-{4-[4-(1-methyl- 0.000336 >64.0 1 8 21H-pyrazol-5-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 25(2R)-N-hydroxy-2-methyl-4-{4-[4-(2-methyl- 0.000298 >64.0 1 2 21,3-oxazol-4-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 26(2R)-N-hydroxy-2-methyl-4-{4-[4-(5-methyl- 0.0371,2,4-oxadiazol-3-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 27(2R)-N-hydroxy-2-methyl-4-{4-[4-(2- 0.000256 >64.0 16 32 4methylpyrimidin-5-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 28(2R)-4-{4-[4-(difluoromethoxy)-2- 0.0000364 >64.0 0.25 1 0.5fluorophenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 29N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2- <0.00100 >64.0 0.5 2 4oxo-4-[4-(pyridin-2-yloxy)phenyl]pyridin- 1(2H)-yl}butanamide 30N-hydroxy-4-{4-[4-(3-hydroxypropoxy)phenyl]- 0.000152 >64.0 2 16 42-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl) butanamide 31N-hydroxy-4-{4-[4-(3-hydroxypropyl)phenyl]- 0.000267 >64.0 8 16 42-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl)butanamide 32(2R)-N-hydroxy-4-[4-{4-[2-(3- 0.0000118 >64.0 0.25 1 1hydroxycyclobutyl)ethoxy]phenyl}-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 334-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)- 0.000625 >64.0 1 4 2yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 34N-hydroxy-4-[4-(6-methoxy-2-naphthyl)-2- 0.000094 8 <0.0600 0.5 1oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 35N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2- 0.000107 >64.0 0.5 4 2oxo-4-(4-pyridin-4-ylphenyl)pyridin-1(2H)- yl]butanamide 36N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2- 0.000912 >64.0 4 8 8oxo-4-quinolin-7-ylpyridin-1(2H)-yl)butanamide 37N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2- 0.000055 >64.0 0.5 2 4oxo-4-[4-(2-pyridin-4-ylethoxy)phenyl]pyridin- 1(2H)-yl}butanamide 38(2R)-N-hydroxy-2-methyl-4-{4-[4-(5-methyl- 0.0000233 >64.0 0.06 0.1250.5 1,3-oxazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 39 (2R)-N-hydroxy-2-methyl-2-0.000142 >64.0 0.5 1 2 (methylsulfonyl)-4-[2-oxo-4-(4-pyrimidin-2-ylphenyl)pyridin-1(2H)-yl]butanamide 40 (2R)-N-hydroxy-2-methyl-2-0.0000482 >64.0 0.03 0.06 0.25 (methylsulfonyl)-4-{2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)- yl}butanamide 41(2R)-4-[4-(4-fluorophenyl)-2-oxopyridin- 0.0000322 >64.0 1 4 0.51(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 42(2R)-4-[4-(3-fluorophenyl)-2-oxopyridin- 0.0000569 >64.0 2 4 11(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 43(2R)-4-[4-(2-fluorophenyl)-2-oxopyridin- 0.00011 >64.0 1 2 0.51(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 44(2R)-4-[4-(2,3-difluoro-4-methoxyphenyl)-2- 0.000166 >64.0 0.015 2 1oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 45(2R)-4-[4-(3-chloro-2-fluorophenyl)-2- 0.000112 >64.0 0.25 0.5 0.5oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 46(2R)-4-[4-(2,3-dichlorophenyl)-2-oxopyridin- 0.000107 >64.0 0.25 0.5 0.51(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 47(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)- 0.000352 >64.0 0.5 4 24-{2-oxo-4-[4-(tetrahydro-2H-pyran-4-yl)phenyl]pyridin-1(2H)-yl}butanamide 48(2R)-N-hydroxy-4-[4-{4-[(2-methoxyethyl)thio]phenyl}- 0.0000561 >64.00.25 1 1 2-oxopyridin-1(2H)-yl]-2- methyl-2-(methylsulfonyl)butanamide49 (2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2- 0.000133 >64.0 0.125 0.250.25 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 50(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)- 0.000133 64 0.5 1 0.54-[2-oxo-4-(2,3,4-trifluorophenyl)pyridin- 1(2H)-yl]butanamide 514-[4-(benzyloxy)-2-oxopyridin-1(2H)-yl]-N- >64.0 16 32 16hydroxy-2-methyl-2-(methylsulfonyl)butanamide 52N-hydroxy-2-methyl-4-(3-methyl-2-oxo-4- >64.0 2 4 4phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanamide 534-(4-cyclohexyl-2-oxopyridin-1(2H)-yl)-N- >64.0 16 64 8hydroxy-2-methyl-2-(methylsulfonyl)butanamide 542-ethyl-N-hydroxy-2-(methylsulfonyl)-4-(2- 64 16 >64.0 16oxo-4-phenylpyridin-1(2H)-yl)butanamide 55(2R)-4-(3-fluoro-2-oxo-4-phenylpyridin- 0.000606 >64.0 8 8 11(2H)-yl)-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 56(2R)-4-(5-fluoro-2-oxo-4-phenylpyridin- 0.000455 >64.0 4 4 11(2H)-yl)-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 572-(ethylsulfonyl)-N-hydroxy-2-methyl-4-(2- 16 8 16 64oxo-4-phenylpyridin-1(2H)-yl)butanamide 58(2R)-N-hydroxy-4-{4-[4-(4-methoxy-2H- 0.000125 >64.0 0.03 0.25 0.51,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 59(2R)-N-hydroxy-4-[4-(4-{[(6-methoxypyridin- 0.0000864 >64.0 0.25 0.5 13-yl)oxy]methyl}phenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 60(2R)-4-[4-{4-[difluoro(trans-4- 0.0000838 32 0.125 1 1hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 61(2R)-N-hydroxy-4-[4-{4-[4- 0.000454 >64.0 64 8 2(hydroxymethyl)piperidin-1-yl]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 62N-hydroxy-4-[4-{4-[(1E)-N- >64.0 0.5 2 4methoxyethanimidoyl]phenyl}-2-oxopyridin- 1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 63N-hydroxy-4-[4-{4-[3-(hydroxymethyl)isoxazol- >64.0 2 16 45-yl]-3-methylphenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 64(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)- 0.00078 >64.0 8 16 84-[2-oxo-4-(3-phenylazetidin-1-yl)pyridin- 1(2H)-yl]butanamide 65(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)- 0.000239 64 0.125 0.25 0.54-[2-oxo-4-(phenylethynyl)pyridin-1(2H)- yl]butanamide 664-[4-(3-cyclohexylpropoxy)-2-oxopyridin- 0.0035 2 1 4 81(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 67(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)- 0.00301 >64.0 8 16 84-(2-oxo-1′-pyrimidin-2-yl-1′,2′,3′,6′- tetrahydro-4,4′-bipyridin-1(2H)-yl)butanamide 68-A (2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-0.000156 >64.0 0.06 0.5 0.5 4-[4-(2-naphthyl)-2-oxopyridin-1(2H)-yl]butanamide 68-B (2R)-4-[4-(4-chloro-3-fluorophenyl)-2-0.0000886 >64.0 0.5 2 0.5 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 68-C(2R)-4-[4-(3,4-dichlorophenyl)-2-oxopyridin- 0.000119 >64.0 0.125 0.50.5 1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 68-D(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)- 0.000176 >64.0 0.06 0.1250.5 4-{2-oxo-4-[4-(1,3-thiazol-2- yl)phenyl]pyridin-1(2H)-yl}butanamide68-E (2R)-4-[4-(2-chloro-3-methylphenyl)-2- 0.000433 64 0.25 0.5 0.5oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide68-F (2R)-N-hydroxy-4-[4-(4-isoxazol-3- 0.000118 >64.0 0.25 0.5 0.5ylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide68-G (2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)- 0.0000135 >64.0 0.5 2 14-[2-oxo-4-(4-propionylphenyl)pyridin- 1(2H)-yl]butanamide 68-H(2R)-N-hydroxy-4-{4-[4-(cis-3-hydroxy-3- 0.000205 >64.0 2 8 1methylcyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 68-I(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)- 0.0000256 >64.0 1 4 14-{2-oxo-4-[4-(trifluoromethyl)phenyl]pyridine- 1(2H)-yl}butanamide 68-J(2R)-N-hydroxy-2-methyl-4-{3-methyl-2- 0.000298 >64.0 0.125 0.125 1oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 68-K(2R)-4-(4-cyclohex-1-en-1-yl-2-oxopyridin- >64.0 4 8 11(2H)-yl)-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 68-L(2R)-4-(4-cyclohept-1-en-1-yl-2-oxopyridin- >64.0 2 8 11(2H)-yl)-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 68-M(2R)-N-hydroxy-4-[4-{4-[(3- 0.0000856 >64.0 0.5 4 2hydroxycyclobutyl)methyl]phenyl}-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 68-N (2R)-N-hydroxy-4-[4-{6-[(1S)-1-0.0000824 >64.0 0.5 4 2 hydroxyethyl]-2-naphthyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 68-ON-hydroxy-4-[4-(6-hydroxy-5,6,7,8- >64.0 16 64 8tetrahydronaphthalen-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 68-P(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)- 0.000263 >64.0 0.06 0.5 84-[2-oxo-4-(5-phenyl-2-thienyl)pyridin- 1(2H)-yl]butanamide 68-QN-hydroxy-4-{4-[4-(1-hydroxyethyl)phenyl]- >64.0 64 >64.0 162-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl)butanamide 68-RN-hydroxy-2-methyl-4-[4-(1-methyl-1H- >64.0 4 4 8indol-2-yl)-2-oxopyridin-1(2H)-yl]-2- (methylsulfonyl)butanamide 68-S4-[4-(2-cyclopentylethoxy)-2-oxopyridin- 0.00894 64 16 64 321(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 68-T(2R)-4-(4-cyclohex-1-en-1-yl-2-oxopyridin- >64.0 4 8 11(2H)-yl)-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 68-UN-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2- 0.0332 >64.0 32 64 64oxo-4-(2-phenylethoxy)pyridin-1(2H)- yl]butanamide 68-V4-[4-(4-acetylphenyl)-2-oxopyridin-1(2H)-yl]- >64.0 4 8 4N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Examples 69 to 488

The following compounds can be made following the general proceduresoutlined in Examples 1-68 in above. Products are typically derived froma Suzuki-Miyaura cross coupling with optional deprotection of a terminalhydroxamic acid protecting group. Methods used to describe the synthesisof the precursors or coupling partners such as boronic acids or estesrare known to those skilled in the art.

In Table 5 below, column 2 provides the IUPAC name, column's 3-7 providein-vitro biological data generated in the same manner as in Table 4,columns 8 and 10 provide the retention times and mass spectra generatedvia LCMS, using either Method A or B as described below. Data is notcurrently available for all compounds, as indicated by a blank cell inTable 5.

The LCMS retention times (LCMS-RT) reported in column 9 were generatedin the following manner:

1) Acidic-labelled as “^(a)” in Column 9

-   Gradients:-   0.05% TFA 95 5 to 5 95 Water ACN-   Flow rate: 1.3 mL/min-   Column dimensions: Acquity UPLC BEH C18 1.7 μm 2.1×30 mm.-   Run time: 1.1 minutes    2) Basic-labelled as “^(b)” in Column 9-   Gradients:-   Solvent A: 0.06% NH₄OH (in water)-   Solvent B: 0.06% NH₄OH (in acetonitrile)

Time (min) % A % B 0 95 5 0.4 95 5 3.2 5 95 3.5 5 95 4.0 95 5

-   Flow rate: 2 mL/min-   Column dimensions: Not currently available-   Run time: 4 minutes

TABLE 5 Example Retention Number IUPACNAME PA:IC50 AB-3167: EC-1 KP-3700PA-7 Time Method MASS 69 4-{4-[4-(1,1-difluoro-2-hydroxyethyl)phenyl]-0.00133 64 4 >64.0 16 0.32 a 445.1 2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 704-[4-(3-fluoro-4-hydroxyphenyl)-2- 0.00397 >64.0 >64.0 >64.0 >64.0 0.29a 399 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 71 N-hydroxy-2-methyl-2-0.000699 >64.0 2 8 4 0.26 a 508.1 (methylsulfonyl)-4-{4-[4-(3-morpholin-4-ylpropoxy)phenyl]-2- oxopyridin-1(2H)-yl}butanamide 72N-hydroxy-4-{4-[4-(hydroxymethyl)phenyl]- 0.00164 >64.0 >64.0 >64.0 160.26 a 395 2-oxopyridin-1(2H)-yl}-2- methyl-2-(methylsulfonyl)butanamide73 4-[4-(4-glycoloylphenyl)-2-oxopyridin- 0.00163 >64.0 >64.0 >64.0 640.27 a 423.1 1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide74 N-hydroxy-2-methyl-2- 0.00316 >64.0 >64.0 >64.0 >64.0 0.26 a 478.1(methylsulfonyl)-4-{2-oxo-4-[4-(2- pyrrolidin-1-ylethoxy)phenyl]pyridin-1(2H)-yl}butanamide 75 N-hydroxy-4-{4-[4-(4-hydroxybutoxy)phenyl]-0.0000945 >64.0 2 4 4 0.33 a 453.2 2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 764-{4-[3-fluoro-4-(2-hydroxyethoxy)phenyl]- 0.000599 >64.0 16 64 32 0.29a 443.1 2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 77 N-hydroxy-2-methyl-2-0.0033 >64.0 64 >64.0 64 (methylsulfonyl)-4-{2-oxo-4-[4-(3-piperidin-1-ylpropoxy)phenyl]pyridin- 1(2H)-yl}butanamide 78N-hydroxy-2-methyl-2- 0.00416 >64.0 >64.0 >64.0 >64.0(methylsulfonyl)-4-{2-oxo-4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]pyridin- 1(2H)-yl}butanamide 79N-hydroxy-4-[4-(1H-indol-5-yl)-2- 0.000241 >64.0 4 8 4oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 80N-hydroxy-4-[4-{4-[(1E)-N- 0.0004 >64.0 8 16 32 0.31 a 422.1hydroxyethanimidoyl]phenyl}-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 81 N-hydroxy-2-methyl-2- 0.000572 >64.0 2 4 40.28 a 524.2 (methylsulfonyl)-4-{2-oxo-4-[4-(3- thiomorpholin-4-ylpropoxy)phenyl]pyridin-1(2H)- yl}butanamide 824-[4-{4-[3-(1,1-dioxidothiomorpholin- 0.00111 >64.0 8 64 32 0.26 a 556.24-yl)propoxy]phenyl}-2-oxopyridin- 1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 83 N-hydroxy-4-[4-{4-[3-(4- 0.00157 >64.032 >64.0 16 0.25 a 522.2 hydroxypiperidin-1-yl)propoxy]phenyl}-2-oxopyridin- 1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 84 N-hydroxy-4-[4-{4-[3-(3-0.00345 >64.0 >64.0 >64.0 32 0.25 a 494.2 hydroxyazetidin-1-yl)propoxy]phenyl}-2-oxopyridin- 1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 85 4-{4-[2-fluoro-4-(2- 0.000468 >64.0 16 6416 0.29 a 443.1 hydroxyethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 86N-hydroxy-2-methyl-2- 0.00118 >64.0 16 >64.0 32 0.24 a 521.2(methylsulfonyl)-4-[2-oxo-4-{4-[3-(3- oxopiperazin-1-yl)propoxy]phenyl}pyridin-1(2H)- yl]butanamide 87N-hydroxy-2-methyl-4-[4-{4-[3-(4- 0.00319 >64.0 64 >64.0 32methylpiperazin-1- yl)propoxy]phenyl}-2-oxopyridin- 1(2H)-yl]-2-(methylsulfonyl)butanamide 88 N-hydroxy-2-methyl-2- 0.000141 >64.0 0.252 2 (methylsulfonyl)-4-{2-oxo-4-[4-(3-pyridin-3-ylpropoxy)phenyl]pyridin- 1(2H)-yl}butanamide 89N-hydroxy-2-methyl-2- 0.000104 >64.0 0.25 2 2(methylsulfonyl)-4-{2-oxo-4-[4-(3- pyridin-4-ylpropoxy)phenyl]pyridin-1(2H)-yl}butanamide 90 4-[4-(2-fluoro-3-methoxyphenyl)-2- 0.000147 >64.00.5 2 2 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 91 N-hydroxy-4-[4-(1H-indol-2-yl)-2-0.000752 >64.0 4 32 16 oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 92 N-hydroxy-2-methyl-2- 0.000689 >64.0 8 3216 0.3 a 490.1 (methylsulfonyl)-4-[2-oxo-4-{4-[3- (1H-1,2,4-triazol-1-yl)propoxy]phenyl}pyridin-1(2H)- yl]butanamide 934-[4-{4-[3-(3,3-difluoropyrrolidin-1- 0.000218 >64.0 1 4 8 0.27 a 528.1yl)propoxy]phenyl}-2-oxopyridin- 1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 94 N-hydroxy-2-methyl-2- 0.000768 >64.0 2 164 (methylsulfonyl)-4-{4-[4-(2- morpholin-4-ylethoxy)phenyl]-2-oxopyridin-1(2H)-yl}butanamide 95 N-hydroxy-4-[4-{4-[3- 0.000237 >64.0 816 8 0.3 a 462 (hydroxymethyl)isoxazol-5-yl]phenyl}-2-oxopyridin-1(2H)-yl]-2- methyl-2-(methylsulfonyl)butanamide96 4-[4-(2-fluoro-3-hydroxyphenyl)-2- 0.00127 >64.0 64 >64.0 >64.0oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide 97N-hydroxy-4-[4-(4-hydroxyphenyl)-2- 0.00222 >64.0 >64.0 >64.0 >64.0 0.26a 381.1 oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 98N-hydroxy-2-methyl-2- 0.00412 >64.0 64 >64.0 32 0.35 a 365.1(methylsulfonyl)-4-(2-oxo-4- phenylpyridin-1(2H)-yl)butanamide 994-[4-(4-acetyl-3-hydroxyphenyl)-2- 0.00149 >64.0 8 16 16 0.44 a 423.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide100 4-[4-{4-[3-(3,3-difluoropiperidin-1- 0.000281 >64.0 1 8 8 0.28 a542.1 yl)propoxy]phenyl}-2-oxopyridin- 1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 101 N-hydroxy-2-methyl-2- 0.000153 >64.0 8 84 0.35 a 410 (methylsulfonyl)-4-[4-(4-nitrophenyl)-2-oxopyridin-1(2H)-yl]butanamide 102 N-hydroxy-2-methyl-4-[4-{4-0.00492 >64.0 >64.0 >64.0 >64.0 0.28 a 458[(methylamino)sulfonyl]phenyl}-2- oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide 103N-ethyl-3-fluoro-5-{1-[4- >0.100 >64.0 >64.0 >64.0 >64.0 0.31 a 454.1(hydroxyamino)-3-methyl-3- (methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}benzamide 104 N-hydroxy-2-methyl-4-{4-[4-(1-0.0111 >64.0 >64.0 >64.0 >64.0 0.22 a 445.1methyl-1H-imidazol-2-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 1054-[4-(5-chloro-2-ethoxyphenyl)-2- >0.100 >64.0 >64.0 >64.0 >64.0 0.43 a443 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 106 4-[4-{4-0.00297 >64.0 >64.0 >64.0 64 0.32 a 472.1[(dimethylamino)sulfonyl]phenyl}-2- oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 107 N-hydroxy-2-methyl-2-0.0023 >64.0 32 64 16 0.33 a 371 (methylsulfonyl)-4-[2-oxo-4-(3-thienyl)pyridin-1(2H)-yl]butanamide 1084-[4-(5-amino-2-methylphenyl)-2- >0.100 >64.0 >64.0 >64.0 >64.0 0.22 a394 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 109N-hydroxy-4-(4-isoquinolin-4-yl-2- 0.00733 >64.0 >64.0 >64.0 >64.0 0.22a 416.1 oxopyridin-1(2H)-yl)-2-methyl-2- (methylsulfonyl)butanamide 1104-[4-(3-aminophenyl)-2-oxopyridin- 0.0111 >64.0 >64.0 >64.0 64 0.2 a 3801(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 111N-hydroxy-2-methyl-2- 0.0162 >64.0 >64.0 >64.0 >64.0 0.35 a 431.1(methylsulfonyl)-4-{2-oxo-4-[3-(1H- pyrazol-1-yl)phenyl]pyridin-1(2H)-yl}butanamide 112 4-[4-(3-fluoro-5-methylphenyl)-2- 0.000679 >64.0 4 164 0.39 a 397.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 1134-{1-[4-(hydroxyamino)-3-methyl-3- 0.0211 >64.0 >64.0 >64.0 >64.0 0.24 a422.1 (methylsulfonyl)-4-oxobutyl]-2-oxo- 1,2-dihydropyridin-4-yl}-3-methylbenzamide 114 4-[4-(3-chlorophenyl)-2-oxopyridin- 0.000589 >64.0 28 4 0.39 a 399.1 1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 115 4-[4-(3-amino-4-methylphenyl)-2-0.00101 >64.0 64 64 16 0.23 a 394 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 1164-[6-(dimethylamino)-2′-oxo-3,4′- 0.00699 >64.0 16 32 64 0.2 a 409.1bipyridin-1′(2′H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide117 4-[4-(5-fluoro-2-hydroxyphenyl)-2- 0.00472 >64.0 >64.0 >64.0 >64.00.32 a 399.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 1184-[4-(3-furyl)-2-oxopyridin-1(2H)-yl]- 0.0235 >64.0 >64.0 >64.0 64 0.29a 355.2 N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 1194-[4-(4-cyclohexylphenyl)-2- 0.000135 16 0.5 8 16 0.54 a 447.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide120 N-hydroxy-4-[4-(2-methoxyphenyl)-2- 0.003 >64.0 64 >64.0 16 0.35 a395.1 oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 1214-[4-(3-chloro-5-fluorophenyl)-2- 0.000583 >64.0 8 32 16 0.4 a 417.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide122 4-[4-(4-fluoro-2-methylphenyl)-2- 0.000785 >64.0 16 64 8 0.38 a397.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 1234-[4-(2,3-difluoro-4-methoxyphenyl)- 0.00022 >64.0 2 8 2 0.37 a 431.12-oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide124 N-hydroxy-2-methyl-2- 0.000962 >64.0 16 64 16 0.26 a 416.1(methylsulfonyl)-4-(2-oxo-4-quinolin- 3-ylpyridin-1(2H)-yl)butanamide125 N-hydroxy-2-methyl-2- 0.00196 >64.0 16 64 32 0.26 a 416.1(methylsulfonyl)-4-(2-oxo-4-quinolin- 3-ylpyridin-1(2H)-yl)butanamide126 N,N-diethyl-4-{1-[4-(hydroxyamino)- 0.00562 >64.0 >64.0 >64.0 >64.00.34 a 464.1 3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4- yl}benzamide 1274-[4-(3-acetylphenyl)-2-oxopyridin- 0.00312 >64.0 16 64 32 0.32 a 407.11(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 1284-[4-(7-chlorothieno[3,2-b]pyridin-2- 0.00203 >64.0 32 64 64 0.36 a455.9 yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy- 2-methyl-2-(methylsulfonyl)butanamide 129 4-{4-[4-(cyanomethyl)phenyl]-2-0.000695 >64.0 2 16 32 0.31 a 404.1 oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 130 N-hydroxy-2-methyl-2-0.000973 >64.0 16 32 8 0.4 a 419.1 (methylsulfonyl)-4-[2-oxo-4-(3,4,5-trifluorophenyl)pyridin-1(2H)- yl]butanamide 131N-hydroxy-2-methyl-2- >0.100 >64.0 >64.0 >64.0 >64.0 0.39 a 463(methylsulfonyl)-4-{2-oxo-4-[2-(2,2,2-trifluoroethoxy)phenyl]pyridin-1(2H)- yl}butanamide 1324-[4-(2-cyanophenyl)-2-oxopyridin- 0.0451 >64.0 >64.0 >64.0 >64.0 0.31 a390.1 1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 1334-[4-(3-acetamidophenyl)-2- 0.0768 >64.0 >64.0 >64.0 >64.0 0.28 a 422.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide134 4-[4-(3,4-difluorophenyl)-2- 0.000243 >64.0 4 8 4 0.37 a 401.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide135 4-[4-(4-chloro-3-cyanophenyl)-2- 0.000536 >64.0 16 64 16 0.37 a 424oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide136 4-{4-[4-(ethylsulfonyl)phenyl]-2- 0.00236 >64.0 >64.0 >64.0 64 0.29a 457 oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 137 4-{4-[5-fluoro-2-0.0682 >64.0 >64.0 >64.0 >64.0 0.41 a 467 (trifluoromethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide138 4-[4-(3,4-dimethoxyphenyl)-2- 0.00391 >64.0 64 >64.0 64 0.32 a 425.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide139 N-hydroxy-4-{4-[4-(4- 0.000116 64 0.125 0.5 8 0.46 a 487methoxyphenoxy)phenyl]-2- oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 1404-[4-(2-acetylphenyl)-2-oxopyridin- >0.100 >64.0 >64.0 >64.0 >64.0 0.31a 407.1 1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 1414-[4-(4-chlorophenyl)-2-oxopyridin- 0.000161 >64.0 1 4 1 0.52 a 399.11(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 1424-[4-(4-chloro-3-fluorophenyl)-2- 0.0000468 >64.0 1 2 1 0.53 a 417.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide143 N-hydroxy-2-methyl-2- 0.000584 >64.0 4 16 8 0.41 a 433.1(methylsulfonyl)-4-{2-oxo-4-[3- (trifluoromethyl)phenyl]pyridin-1(2H)-yl}butanamide 144 N-hydroxy-4-{4-[3- 0.0111 >64.0 >64.0 >64.0 >64.0 0.27a 395.1 (hydroxymethyl)phenyl]-2-oxopyridin- 1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 145 N-hydroxy-2-methyl-2- 0.000326 >64.0 1 42 0.43 a 449 (methylsulfonyl)-4-{2-oxo-4-[4-(trifluoromethoxy)phenyl]pyridin- 1(2H)-yl}butanamide 1464-{1-[4-(hydroxyamino)-3-methyl-3- 0.00663 >64.0 >64.0 >64.0 >64.0 0.31a 450.1 (methylsulfonyl)-4-oxobutyl]-2-oxo- 1,2-dihydropyridin-4-yl}-N-isopropylbenzamide 147 4-[4-(2,3-difluorophenyl)-2- 0.000198 >64.0 2 4 10.36 a 401.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 148 4-[4-{3- 0.00761 >64.0 6464 >64.0 0.33 a 472.1 [(dimethylamino)sulfonyl]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide149 4-[4-(5-cyano-2-thienyl)-2-oxopyridin- 0.00081 >64.0 16 32 16 0.31 a396.1 1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 1504-[4-(5-chloro-2-fluorophenyl)-2- 0.000355 >64.0 4 16 4 0.39 a 417oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide151 4-[4-(3-fluoro-4-methylphenyl)-2- 0.000253 >64.0 2 4 2 0.52 a 397.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide152 N-hydroxy-2-methyl-2- 0.0417 >64.0 >64.0 >64.0 >64.0 0.3 a 397(methylsulfonyl)-4-[2-oxo-4-(1-propyl- 1H-pyrazol-4-yl)pyridin-1(2H)-yl]butanamide 153 4-[4-(3-fluoro-2-methylphenyl)-2- 0.000617 >64.0 32 648 0.39 a 397 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 154N-tert-butyl-1′-[4-(hydroxyamino)-3- >0.100 >64.0 >64.0 >64.0 >64.0 0.3a 465.1 methyl-3-(methylsulfonyl)-4-oxobutyl]-2′-oxo-1′,2′-dihydro-3,4′- bipyridine-5-carboxamide 1554-[4-(2-chloro-4-fluorophenyl)-2- 0.000322 >64.0 4 8 0.5 0.39 a 417.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide156 N-hydroxy-2-methyl-2- 0.000481 32 <0.0600 0.25 4 0.46 a 457.1(methylsulfonyl)-4-[2-oxo-4-(4- phenoxyphenyl)pyridin-1(2H)-yl]butanamide 157 4-[4-(2-chloro-3-fluorophenyl)-2- 0.00035 >64.0 4 8 20.38 a 417 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 158N-hydroxy-2-methyl-4-[4-(5-methyl-2- 0.0591 >64.0 64 >64.0 64 afuryl)-2-oxopyridin-1(2H)-yl]-2- (methylsulfonyl)butanamide 1594-[4-(2-fluorophenyl)-2-oxopyridin- 0.000291 >64.0 2 8 2 0.35 a 383.11(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 1604-[4-{5-[(dimethylamino)sulfonyl]-2- >0.100 >64.0 >64.0 >64.0 >64.0 0.35a 486.1 methylphenyl}-2-oxopyridin-1(2H)-yl]- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 161 4-[4-(2,4-dimethoxyphenyl)-2-0.00113 >64.0 8 32 8 0.37 a 425.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 162N-hydroxy-2-methyl-4-[4-(2-methyl-3- 0.0326 >64.0 >64.0 >64.0 >64.0 0.28a 434.1 oxo-2,3-dihydro-1H-isoindol-5-yl)-2- oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide 163 4-[4-(2,3-dichlorophenyl)-2-0.0000992 >64.0 0.5 1 1 0.42 a 432.9 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 1644-[4-(2,3-dihydro-1-benzofuran-5-yl)- 0.00122 >64.0 8 32 32 0.35 a 4072-oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide165 4-[4-(1-benzyl-1H-pyrazol-4-yl)-2- 0.0746 >64.0 >64.0 >64.0 >64.00.35 a 445.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 1664-[4-(4-fluoro-2-methoxyphenyl)-2- 0.00117 >64.0 16 32 8 0.37 a 413oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide167 4-[4-(5-acetyl-2-thienyl)-2-oxopyridin- 0.000891 >64.0 16 32 16 0.31a 412.9 1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 168N-hydroxy-4-(2-isopropoxy-2′-oxo- >0.100 >64.0 >64.0 >64.0 >64.0 0.38 a424.1 3,4′-bipyridin-1′(2′H)-yl)-2-methyl-2- (methylsulfonyl)butanamide169 4-[4-(3-cyanophenyl)-2-oxopyridin- 0.00549 >64.0 >64.0 >64.0 64 0.32a 390 1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 170N-hydroxy-4-[4-(4-methoxyphenyl)-2- 0.00039 >64.0 1 2 1 0.45 a 395.1oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 1714-[4-(5-fluoro-2-methylphenyl)-2- 0.00965 >64.0 64 >64.0 32 0.39 a 397oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide172 N-hydroxy-2-methyl-4-{4-[3-(1- 0.0841 >64.0 >64.0 >64.0 >64.0 0.28 b445.1 methyl-1H-imidazol-2-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 173 4-[4-(5-fluoro-2-methoxyphenyl)-2-0.0114 >64.0 64 >64.0 64 0.37 a 413 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 1744-{4-[2,4-bis(trifluoromethyl)phenyl]- 0.0154 >64.0 64 >64.0 >64.0 0.46a 501 2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 1754-[4-(2-furyl)-2-oxopyridin-1(2H)-yl]- 0.0066 >64.0 64 >64.0 16 0.3 a355 N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 176N-hydroxy-4-[4-(1H-indol-6-yl)-2- 0.000709 >64.0 8 16 4 0.36 a 404oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 177N-ethyl-2-fluoro-4-{1-[4- 0.00201 >64.0 >64.0 >64.0 64 0.3 a 454(hydroxyamino)-3-methyl-3- (methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}benzamide 178 N-hydroxy-2-methyl-4-[4-(3-0.000473 >64.0 4 8 2 0.39 a 379.1 methylphenyl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide 179 N-hydroxy-2-methyl-4-[4-(2-methyl-1-0.00418 >64.0 >64.0 >64.0 >64.0 0.26 a 434oxo-2,3-dihydro-1H-isoindol-5-yl)-2- oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide 180 4-[4-(3-fluoro-4-methoxyphenyl)-2-0.000481 >64.0 2 8 8 0.36 a 413.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 1814-[6-(cyclohexylmethoxy)-2′-oxo-3,4′- 0.000199 64 0.125 1 4 0.52 a 478.2bipyridin-1′(2′H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide182 N-hydroxy-4-(2-methoxy-2′-oxo-3,4′- 0.0142 >64.0 >64.0 >64.0 64 0.3a 396 bipyridin-1′(2′H)-yl)-2-methyl-2- (methylsulfonyl)butanamide 183N-hydroxy-2-methyl-2- 0.00413 >64.0 32 >64.0 32 0.39 a 433(methylsulfonyl)-4-{2-oxo-4-[2- (trifluoromethyl)phenyl]pyridin-1(2H)-yl}butanamide 184 4-[4-(4-ethoxy-3-fluorophenyl)-2- 0.000223 >64.0 0.5 22 0.39 a 427 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 1854-(6-ethoxy-2′-oxo-3,4′-bipyridin- 0.000388 >64.0 2 4 4 0.33 a 4101′(2′H)-yl)-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 1864-[4-(2,4-difluorophenyl)-2- 0.000173 >64.0 2 4 2 0.47 a 401.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide187 4-[4-(3-fluorophenyl)-2-oxopyridin- 0.000658 >64.0 8 16 2 0.36 a 3831(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 1884-{1-[4-(hydroxyamino)-3-methyl-3- 0.0104 >64.0 >64.0 >64.0 >64.0 0.25 a422.1 (methylsulfonyl)-4-oxobutyl]-2-oxo- 1,2-dihydropyridin-4-yl}-N-methylbenzamide 189 N-hydroxy-2-methyl-2- 0.0038 >64.0 >64.0 >64.0 640.26 a 416 (methylsulfonyl)-4-(2-oxo-4-quinolin-8-ylpyridin-1(2H)-yl)butanamide 190 N-hydroxy-2-methyl-4-[4-(4-0.000281 >64.0 1 4 1 0.5 a 379.1 methylphenyl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide 191N-hydroxy-4-{4-[2- >0.100 >64.0 >64.0 >64.0 >64.0 0.35 a 409(methoxymethyl)phenyl]-2- oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 192 4-[4-(4-fluorophenyl)-2-oxopyridin-0.00078 >64.0 8 8 2 0.36 a 383 1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 193 4-[4-(4-fluoro-3-methylphenyl)-2-0.0000495 >64.0 2 8 2 0.4 a 397 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 1944-[4-(5-cyano-1-methyl-1H-pyrrol-2- 0.0166 >64.0 >64.0 >64.0 >64.0 0.32a 393.1 yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy- 2-methyl-2-(methylsulfonyl)butanamide 195 4-[4-(2,5-dimethoxyphenyl)-2-0.0565 >64.0 >64.0 >64.0 >64.0 0.36 a 425.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide196 4-[4-(2,5-difluorophenyl)-2- 0.000763 >64.0 8 16 4 0.36 a 401oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide197 4-[4-(2-fluorobiphenyl-4-yl)-2- 0.000115 16 0.25 0.5 2 0.47 a 459oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide198 4-[4-(4-cyanophenyl)-2-oxopyridin- 0.000456 >64.0 16 32 8 0.32 a 3901(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 1994-[4-(4-butylphenyl)-2-oxopyridin- 0.0000867 32 0.125 0.5 2 0.5 a 4211(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 200N-hydroxy-4-(6-methoxy-2-methyl-2′- 0.00365 >64.0 32 64 16 0.27 a 410.1oxo-3,4′-bipyridin-1′(2′H)-yl)-2- methyl-2-(methylsulfonyl)butanamide201 N-hydroxy-2-methyl-4-[4-(2- 0.00612 >64.0 32 64 16 0.38 a 379.1methylphenyl)-2-oxopyridin-1(2H)-yl]- 2-(methylsulfonyl)butanamide 2013-fluoro-5-{1-[4-(hydroxyamino)-3- >0.100 >64.0 >64.0 >64.0 >64.0 0.29 a440.1 methyl-3-(methylsulfonyl)-4- oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}-N-methylbenzamide 203 N-hydroxy-2-methyl-4-[4-(5-methyl-1-0.0304 >64.0 64 >64.0 >64.0 0.36 a 445phenyl-1H-pyrazol-4-yl)-2-oxopyridin- 1(2H)-yl]-2-(methylsulfonyl)butanamide 204 4-[4-(2-chloro-5-hydroxyphenyl)-2-0.0168 >64.0 64 >64.0 >64.0 0.33 a 415 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 2054-(2-ethoxy-2′-oxo-3,4′-bipyridin- >0.100 >64.0 >64.0 >64.0 >64.0 0.34 a410 1′(2′H)-yl)-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 206N-hydroxy-4-[4-(3-methoxyphenyl)-2- 0.000574 16 4 8 4 0.36 a 395oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 2074-[4-(4-cyano-3-fluorophenyl)-2- 0.000756 >64.0 16 >64.0 16 0.34 a 408oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide208 4-[4-(4-fluoro-3-methoxyphenyl)-2- 0.00148 >64.0 32 64 16 0.37 a 413oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide209 N-hydroxy-2-methyl-4-(2′-methyl-2- 0.00428 >64.0 64 >64.0 32 0.16 a380 oxo-4,4′-bipyridin-1(2H)-yl)-2- (methylsulfonyl)butanamide 210N-hydroxy-4-[4-(3-hydroxyphenyl)-2- 0.00151 >64.0 >64.0 >64.0 >64.0 0.29a 381.1 oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 211N-tert-butyl-2-fluoro-5-{1-[4- 0.0486 >64.0 64 >64.0 >64.0 0.39 a 482.1(hydroxyamino)-3-methyl-3- (methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}benzamide 212N-hydroxy-2-methyl-2- >0.100 >64.0 >64.0 >64.0 >64.0 0.34 a 455(methylsulfonyl)-4-[2-oxo-4-(3,4,5- trimethoxyphenyl)pyridin-1(2H)-yl]butanamide 213 N-hydroxy-4-[4-(2-hydroxyphenyl)-2-0.015 >64.0 >64.0 >64.0 >64.0 0.3 a 381 oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 214 4-[4-(3-chloro-4-fluorophenyl)-2-0.000172 >64.0 1 4 2 0.41 a 417 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 215N-hydroxy-4-(4-isoquinolin-5-yl-2- 0.00402 >64.0 >64.0 >64.0 64 0.21 a416.1 oxopyridin-1(2H)-yl)-2-methyl-2- (methylsulfonyl)butanamide 2164-[4-(3,5-dichlorophenyl)-2- 0.00135 >64.0 4 16 8 0.44 a 432.9oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide217 N-hydroxy-2-methyl-2- 0.000341 8 <0.0600 1 8 0.54 a 435.1(methylsulfonyl)-4-[2-oxo-4-(4- pentylphenyl)pyridin-1(2H)-yl]butanamide 218 N-hydroxy-2-methyl-2- 0.00793 >64.0 >64.0 >64.0 640.12 a 366 (methylsulfonyl)-4-(2-oxo-4,4′- bipyridin-1(2H)-yl)butanamide219 N-hydroxy-2-methyl-2- 0.0599 >64.0 >64.0 >64.0 >64.0 0.13 a 366(methylsulfonyl)-4-(2′-oxo-3,4′- bipyridin-1′(2′H)-yl)butanamide 220N-hydroxy-2-methyl-4-(6-methyl-2- 0.0386 >64.0 >64.0 >64.0 >64.0 0.38 a379.1 oxo-4-phenylpyridin-1(2H)-yl)-2- (methylsulfonyl)butanamide 2214-{4-[3-chloro-4-(3-morpholin-4- 0.00037 >64.0 2 16 8 0.28 a 542.2ylpropoxy)phenyl]-2-oxopyridin- 1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 222 N-hydroxy-2-methyl-4-{4-[3-methyl-4-0.00036 >64.0 2 16 8 0.28 a 522.2 (3-morpholin-4-ylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2- (methylsulfonyl)butanamide 2234-{4-[3-fluoro-4-(3-morpholin-4- 0.000651 >64.0 4 32 8 0.26 a 526.2ylpropoxy)phenyl]-2-oxopyridin- 1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 224 N-hydroxy-4-{4-[4-(2- 0.00122 >64.0 32 648 0.31 a 423.1 hydroxypropyl)phenyl]-2-oxopyridin- 1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 225 4-{4-[2-chloro-4-(3-morpholin-4-0.000496 >64.0 8 32 16 0.28 a 542.1 ylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 2264-{4-[2-fluoro-4-(3-morpholin-4- 0.000563 >64.0 2 16 8 0.26 a 526.1ylpropoxy)phenyl]-2-oxopyridin- 1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 227 N-hydroxy-4-{4-[3-methoxy-4-(3-0.00616 >64.0 64 >64.0 64 0.26 a 538.1 morpholin-4-ylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl)butanamide 228N-hydroxy-2-methyl-4-{4-[2-methyl-4- 0.000756 >64.0 8 32 16 0.27 a 522.1(3-morpholin-4-ylpropoxy)phenyl]-2- oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 229 N-hydroxy-4-[4-{4-[(5- 0.00021 >64.0 0.252 2 0.34 a 467.1 hydroxypentyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 2304-{4-[4-(aminosulfonyl)phenyl]-2- 0.00897 >64.0 64 >64.0 >64.0 0.24 a444 oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 231 N-hydroxy-4-{4-[3-(2-0.0102 >64.0 >64.0 >64.0 >64.0 0.32 a 423.1hydroxypropyl)phenyl]-2-oxopyridin- 1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 232 4-{4-[2-chloro-4-(2- 0.000339 >64.0 16 3216 0.3 a 459 hydroxyethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 233N-hydroxy-4-{4-[4-(2-hydroxyethoxy)- 0.0361 >64.0 >64.0 >64.0 >64.0 0.32a 453.1 2,5-dimethylphenyl]-2-oxopyridin- 1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 234 4-{4-[2,3-dichloro-4-(2- 0.00141 >64.0 6464 32 0.34 a 493 hydroxyethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 235N-hydroxy-4-{4-[4-(2-hydroxyethoxy)- 0.000618 >64.0 8 32 8 0.31 a 439.13-methylphenyl]-2-oxopyridin-1(2H)- yl}-2-methyl-2-(methylsulfonyl)butanamide 236 4-{4-[3-chloro-4-(2- 0.000902 >64.0 32 6416 0.31 a 459 hydroxyethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 237N-hydroxy-4-{4-[4-(2-hydroxyethoxy)- 0.00349 >64.0 >64.0 >64.0 32 0.29 a439.1 2-methylphenyl]-2-oxopyridin-1(2H)- yl}-2-methyl-2-(methylsulfonyl)butanamide 238 4-{4-[3-chloro-4-(4- 0.000195 >64.0 0.5 44 0.35 a 487 hydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 2394-{4-[2-chloro-4-(4- 0.000247 >64.0 1 2 4 0.35 a 487hydroxybutoxy)phenyl]-2-oxopyridin- 1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 240 4-{4-[3-fluoro-4-(4- 0.000115 >64.0 1 8 40.33 a 471.1 hydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 2414-{4-[2-fluoro-4-(4- >64.0 2 8 2 hydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 242N-hydroxy-4-{4-[4-(4-hydroxybutoxy)- 0.00132 >64.0 32 >64.0 64 0.31 a483.1 3-methoxyphenyl]-2-oxopyridin- 1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 243 N-hydroxy-4-{4-[4-(4-hydroxybutoxy)-0.000592 >64.0 4 16 8 0.34 a 467.1 2-methylphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl)butanamide 244 4-{4-[2,5-dichloro-4-(2-0.00394 >64.0 32 64 >64.0 0.32 a 493 hydroxyethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 245N-hydroxy-4-{4-[4-(4-hydroxybutoxy)- >64.0 64 >64.0 642-methoxyphenyl]-2-oxopyridin- 1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 246 4-{4-[3-chloro-4-(3- 0.0000842 >64.0 2 84 0.33 a 473 hydroxypropoxy)phenyl]-2- oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 247 4-{4-[3-fluoro-4-(3-0.000416 >64.0 4 16 8 0.31 a 457.1 hydroxypropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide248 N-hydroxy-4-{4-[4-(3- 0.000072 >64.0 2 8 4 0.33 a 453.1hydroxypropoxy)-3-methylphenyl]-2- oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 249 N-hydroxy-4-{4-[4-(3-0.00432 >64.0 >64.0 >64.0 64 0.29 a 469.1hydroxypropoxy)-3-methoxyphenyl]- 2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 250 4-{4-[2-fluoro-4-(3- 0.0000867 >64.0 2 84 0.31 a 457.1 hydroxypropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide251 4-{4-[2-chloro-4-(3- 0.000195 >64.0 2 4 4 0.33 a 473hydroxypropoxy)phenyl]-2- oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 252 N-hydroxy-4-{4-[4-(3-0.000125 >64.0 16 64 16 0.32 a 453.1 hydroxypropoxy)-2-methylphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl)butanamide 253N-hydroxy-4-{4-[4-(3- 0.000236 >64.0 16 64 >64.0 0.31 a 469.1hydroxypropoxy)-2-methoxyphenyl]- 2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 254 N-hydroxy-2-methyl-2- >64.0 4 8 4(methylsulfonyl)-4-(2-oxo-4-quinolin- 6-ylpyridin-1(2H)-yl)butanamide255 N-hydroxy-4-{4-[4-(2-hydroxy-2- 0.00206 >64.0 2 32 8 0.33 a 437.1methylpropyl)phenyl]-2-oxopyridin- 1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 256 N-hydroxy-2-methyl-4-[4-(2-methyl-0.000212 64 1 4 4 0.35 a 418.1 1H-indol-5-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide 257 4-[4-(2,3-dimethylphenyl)-2-0.00055 >64.0 4 8 2 0.41 a 393.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 258 N-hydroxy-4-[4-(6-hydroxy-2-0.000156 >64.0 1 4 2 0.42 a 431.1 naphthyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 259 N-hydroxy-2-methyl-2-0.000252 >64.0 0.5 2 2 0.33 a 442.1 (methylsulfonyl)-4-[2-oxo-4-(4-pyridin-2-ylphenyl)pyridin-1(2H)- yl]butanamide 260N-hydroxy-4-(4-isoquinolin-6-yl-2- 0.000244 >64.0 4 8 4 0.22 a 416.1oxopyridin-1(2H)-yl)-2-methyl-2- (methylsulfonyl)butanamide 261N-hydroxy-4-(4-isoquinolin-7-yl-2- 0.000497 >64.0 8 16 4 0.22 a 416.1oxopyridin-1(2H)-yl)-2-methyl-2- (methylsulfonyl)butanamide 262N-hydroxy-4-{4-[3-(2-hydroxy-2- 0.0117 >64.0 64 >64.0 >64.0 0.34 a 437.1methylpropyl)phenyl]-2-oxopyridin- 1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 263 N-hydroxy-4-{4-[3-(2-hydroxyethyl)-0.0211 >64.0 8 >64.0 >64.0 0.28 a 448.11H-indol-5-yl]-2-oxopyridin-1(2H)-yl}- 2-methyl-2-(methylsulfonyl)butanamide 264 4-[4-(2-fluoro-3-methylphenyl)-2-0.0000564 >64.0 0.5 2 0.5 0.39 a 397.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 265N-hydroxy-4-{4-[1-(2-hydroxyethyl)- 0.000386 >64.0 4 32 16 0.31 a 448.21H-indol-5-yl]-2-oxopyridin-1(2H)-yl}- 2-methyl-2-(methylsulfonyl)butanamide 266 4-[4-(3-chloro-2-methylphenyl)-2-0.00035 >64.0 4 8 4 0.42 a 413.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 267N-hydroxy-4-{4-[1-(3-hydroxypropyl)- 0.000418 >64.0 2 16 8 0.33 a 462.21H-indol-5-yl]-2-oxopyridin-1(2H)-yl}- 2-methyl-2-(methylsulfonyl)butanamide 268 N-hydroxy-2-methyl-2- 0.000143 >64.0 1 42 0.3 a 472.1 (methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-4-ylmethoxy)phenyl]pyridin- 1(2H)-yl}butanamide 269N-hydroxy-2-methyl-2- 0.000205 >64.0 0.5 2 2 0.31 a 472.1(methylsulfonyl)-4-{2-oxo-4-[4- (pyridin-3-ylmethoxy)phenyl]pyridin-1(2H)-yl}butanamide 270 N-hydroxy-2-methyl-2- 0.000115 >64.0 1 2 2 0.33a 472.1 (methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-2-ylmethoxy)phenyl]pyridin- 1(2H)-yl}butanamide 271N-hydroxy-2-methyl-2- 0.000305 >64.0 0.25 1 2 0.32 a 486.1(methylsulfonyl)-4-{2-oxo-4-[4-(2- pyridin-3-ylethoxy)phenyl]pyridin-1(2H)-yl}butanamide 272 N-hydroxy-2-methyl-2- 0.000246 >64.0 0.5 2 20.31 a 486.1 (methylsulfonyl)-4-{2-oxo-4-[4-(2-pyridin-2-ylethoxy)phenyl]pyridin- 1(2H)-yl}butanamide 273N-hydroxy-4-{4-[6-(2-hydroxyethoxy)- 0.000429 >64.0 0.5 4 4 0.42 a 475.22-naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 274 N-hydroxy-4-{4-[6-(3-0.000102 >64.0 0.25 2 2 0.43 a 489.1 hydroxypropoxy)-2-naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl)butanamide 275N-hydroxy-4-[4-(1H-indazol-5-yl)-2- 0.000802 0.32 a 405oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 2764-[4-{4-[4-(aminosulfonyl)butoxy]-2- 0.000925 >64.0 16 32 32 0.42 a550.1 chlorophenyl}-2-oxopyridin-1(2H)-yl]- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 277 N-hydroxy-2-methyl-2- 0.000105 >64.0 1 44 0.36 a 536.2 (methylsulfonyl)-4-[4-{4-[(5-morpholin-4-ylpentyl)oxy]phenyl}-2- oxopyridin-1(2H)-yl]butanamide 2784-{4-[4′-(aminosulfonyl)biphenyl-4- 0.000533 >64.0 2 32 16 0.41 a 520.1yl]-2-oxopyridin-1(2H)-yl}-N-hydroxy- 2-methyl-2-(methylsulfonyl)butanamide 279 (2R)-N-hydroxy-4-{4-[4-(4-0.0000616 >64.0 0.5 4 1 0.41 a 453.2 hydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl)butanamide 280(2R)-N-hydroxy-4-[4-{4-[(5- 0.0000603 >64.0 0.25 1 0.5 0.45 a 467.2hydroxypentyl)oxy]phenyl}-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 281 4-[6-(4-fluorophenyl)-2′-oxo-3,4′-0.000824 >64.0 0.5 4 8 0.46 a 460.1 bipyridin-1′(2′H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 282 4-[4-(4-bromo-3-fluorophenyl)-2-0.0000933 64 0.5 1 1 0.52 a 461 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 283 4-[4-(4-bromo-2-fluorophenyl)-2-0.000226 >64.0 0.25 0.5 1 0.54 a 461 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 284N-hydroxy-2-methyl-4-(5-methyl-2- 0.00892 >64.0 32 64 64 0.47 a 379.1oxo-4-phenylpyridin-1(2H)-yl)-2- (methylsulfonyl)butanamide 285(2R)-N-hydroxy-4-(6-methoxy-2′-oxo- 0.000382 >64.0 4 8 4 0.37 a 396.13,4′-bipyridin-1′(2′H)-yl)-2-methyl-2- (methylsulfonyl)butanamide 286N-hydroxy-4-[4-{4-[3- 0.000403 >64.0 16 32 16 0.41 a 476.1(hydroxymethyl)isoxazol-5-yl]-2- methylphenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 287 N-hydroxy-2-methyl-2-0.000197 >64.0 0.5 4 4 0.4 a 458.1 (methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-3-yloxy)phenyl]pyridin-1(2H)- yl}butanamide 288N-hydroxy-4-[4-(7-methoxy-2- 0.000175 64 0.125 32 4 0.55 a 445.1naphthyl)-2-oxopyridin-1(2H)-yl]-2- methyl-2-(methylsulfonyl)butanamide289 N-hydroxy-2-methyl-2- 0.000601 >64.0 32 64 32 0.4 a 504.2(methylsulfonyl)-4-[4-{2-methyl-4-[3- (1H-1,2,4-triazol-1-yl)propoxy]phenyl}-2-oxopyridin- 1(2H)-yl]butanamide 2904-[4-{3-chloro-4-[3-(1H-1,2,4-triazol- 0.000282 >64.0 16 64 16 0.41 a524.1 1-yl)propoxy]phenyl}-2-oxopyridin- 1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 291 4-[4-{2-chloro-4-[3-(1H-1,2,4-triazol-0.000552 >64.0 16 1 16 0.41 a 524.1 1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 2924-[4-{2,3-dichloro-4-[3-(1H-1,2,4- 0.000193 >64.0 8 32 16 0.45 a 558.1triazol-1-yl)propoxy]phenyl}-2- oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 293 N-hydroxy-2-methyl-2- 0.00031164 4 64 16 0.41 a 504.2 (methylsulfonyl)-4-[4-{3-methyl-4-[3-(1H-1,2,4-triazol-1- yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]butanamide 294 N-hydroxy-2-(methylsulfonyl)-2-[2-(2-0.055 >64.0 >64.0 >64.0 >64.0 0.52 a 393.1 oxo-4-phenylpyridin-1(2H)-yl)ethyl]pentanamide 295 4-[4-(2-fluoro-4-pyridin-3-ylphenyl)-2-0.000133 >64.0 1 2 8 0.31 a 460.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 296N-hydroxy-4-[4-(1H-indol-3-yl)-2- 0.00207 >64.0 64 >64.0 64 0.41 a 404oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 2974-[4-(3-fluoro-4-pyridin-3-ylphenyl)-2- 0.000105 64 1 4 2 0.3 a 460oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide298 4-[4-(3-fluoro-4-pyridin-4-ylphenyl)-2- 0.0000733 >64.0 0.5 4 4 0.29a 460 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 299 N-hydroxy-4-[4-(7-hydroxy-2-0.000238 >64.0 1 8 4 0.43 a 431 naphthyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 300 N-hydroxy-2-methyl-4-[4-(2-0.000599 >64.0 4 16 8 0.26 a 430.1 methylquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-2- (methylsulfonyl)butanamide 301 N-hydroxy-2-methyl-4-[4-(3-0.00111 >64.0 4 16 16 0.28 a 430 methylquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-2- (methylsulfonyl)butanamide 302 N-hydroxy-2-methyl-4-[4-(4-0.00225 >64.0 64 >64.0 16 0.26 a 430 methylquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-2- (methylsulfonyl)butanamide 303(2R)-4-[4-{2,3-dichloro-4-[2-(4- 0.000809 >64.0 32 >64.0 16 0.34 a 576hydroxypiperidin-1-yl)ethoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide304 (2R)-4-{4-[2,3-dichloro-4-(2- 0.000397 >64.0 4 32 16 0.35 a 562morpholin-4-ylethoxy)phenyl]-2- oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 305 N-hydroxy-2-methyl-4-[4-(2-0.00768 >64.0 16 64 >64.0 0.27 a 430.1methylquinolin-7-yl)-2-oxopyridin- 1(2H)-yl]-2-(methylsulfonyl)butanamide 306 4-[4-(7-fluoroisoquinolin-6-yl)-2-0.000323 >64.0 8 4 4 0.3 a 434.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 307 4-{4-[2-fluoro-3-(3-0.000482 >64.0 16 32 16 0.39 a 457.1 hydroxypropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide308 N-hydroxy-2-methyl-4-[4-(3- 0.000465 >64.0 2 4 4 0.32 a 430.1methylquinolin-7-yl)-2-oxopyridin- 1(2H)-yl]-2-(methylsulfonyl)butanamide 309 N-hydroxy-4-{4-[6-(hydroxymethyl)-2-0.000294 >64.0 1 4 4 0.41 a 445.1 naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 310 (2R)-N-hydroxy-4-{4-[4-(6-0.0000406 >16.0 0.125 0.5 0.5 0.51 a 472.2methoxypyridin-3-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 311 (2R)-4-[4-{4-[(1-glycoloylpiperidin-4-0.000149 >64.0 1 8 4 0.42 a 536.2 yl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 312(2R)-4-[4-{4-[2-(1-glycoloylpiperidin- 0.0000768 64 0.5 4 4 0.45 a 550.24-yl)ethoxy]phenyl}-2-oxopyridin- 1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 313 (2R)-4-[4-{4-[3-(1-glycoloylpiperidin-0.000239 64 0.5 2 4 0.48 a 564.2 4-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 314(2R)-N-hydroxy-4-{4-[6-(2- 0.000109 >64.0 0.5 2 1 0.43 a 475.2hydroxyethoxy)-2-naphthyl]-2- oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 315 (2R)-N-hydroxy-4-{4-[6- 0.000147 >64.00.5 1 1 0.41 a 445.1 (hydroxymethyl)-2-naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl)butanamide 316(2R)-4-[4-(3-fluoroquinolin-6-yl)-2- 0.000247 >64.0 4 4 2 0.43 a 434.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide317 (2R)-4-[4-(3-fluoro-4- 0.000156 >64.0 2 4 1 0.46 a 413.1methoxyphenyl)-2-oxopyridin-1(2H)- yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 318 (2R)-4-[4-{3-fluoro-4-[(trans-4-0.0000747 >64.0 0.25 2 1 0.46 a 511.2 hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide319 (2R)-N-hydroxy-4-[4-{4-[(4- >64.0 0.25 1 1hydroxybutyl)thio]phenyl}-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 320 (2R)-4-[4-(4-acetyl-2-fluorophenyl)-2-0.000162 >64.0 1 8 2 0.42 a 425.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 321(2R)-4-[4-(2,4-difluorophenyl)-2- 0.000154 >64.0 1 2 1 0.47 a 401.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide322 (2R)-4-[4-(3-fluoro-4-methylphenyl)- 0.000116 >64.0 0.5 2 0.5 0.51 a397.1 2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 323(2R)-4-[4-(2-fluoro-3-methylphenyl)- 0.0000948 >64.0 0.25 1 0.5 0.52 a397.1 2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 324 (2R)-4-{4-[2-fluoro-4-(4-0.0000758 >64.0 0.25 1 2 0.47 a 485.2 hydroxybutoxy)-3-methylphenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide325 (2R)-4-[4-(4-fluoro-3-methylphenyl)- 0.0000335 64 0.5 2 0.5 0.5 a397.1 2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 326(2R)-4-[4-{2-fluoro-4-[(4-hydroxy-4- 0.000154 >64.0 0.5 2 4 0.48 a 511.2methylcyclohexyl)oxy]phenyl}-2- oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 327 (2R)-N-hydroxy-2-methyl-2-0.00257 >64.0 4 >64.0 >64.0 0.32 a 432.1(methylsulfonyl)-4-[2-oxo-4-(2-oxo- 1,2-dihydroquinolin-6-yl)pyridin-1(2H)-yl]butanamide 328 (2R)-N-hydroxy-4-[4-(2- 0.0000841 >64.0 1 2 10.49 a 446.1 methoxyquinolin-6-yl)-2-oxopyridin- 1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 329 (2R)-N-hydroxy-4-{4-[4-(4- 0.000831 >64.01 32 4 0.28 a 464.2 hydroxypiperidin-1-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl)butanamide 330(2R)-4-[4-(3,4-dihydro-2H-1,5- 0.000541 >64.0 0.5 8 4 0.46 a 437.1benzodioxepin-7-yl)-2-oxopyridin- 1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 331 (2R)-N-hydroxy-2-methyl-2- 0.00629 >64.00.25 64 32 0.44 a 434.1 (methylsulfonyl)-4-[2′-oxo-6-(trifluoromethyl)-3,4′-bipyridin-1′(2′H)- yl]butanamide 332(2R)-4-[4-(4-ethoxyphenyl)-2- 0.0000755 >64.0 64 0.5 0.5 0.5 a 409.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide333 (2R)-4-{4-[4-(cyanomethoxy)phenyl]- 0.000307 >64.0 16 64 8 0.42 a420.1 2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 334 (2R)-4-[4-(3-chloro-4-0.0000985 >64.0 8 4 1 0.49 a 429.1 methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 335(2R)-4-[4-(3,5-difluorophenyl)-2- 0.000502 >64.0 1 8 2 0.48 a 401.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide336 (2R)-4-[4-(3,5-dichlorophenyl)-2- 0.000345 >64.0 4 16 8 0.57 a 433oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide337 (2R)-4-{4-[3-fluoro-4-(piperidin-4- 0.00221 >64.0 >64.0 >64.0 >64.00.32 a 482.2 yloxy)phenyl]-2-oxopyridin-1(2H)-yl}- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 338 (2R)-4-{4-[4- 0.0000528 >64.0 0.5 2 0.50.49 a 431.1 (difluoromethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide339 (2R)-N-hydroxy-2-methyl-2- 0.000378 >64.0 4 16 4 0.39 a 419.1(methylsulfonyl)-4-[2-oxo-4-(1-oxo- 2,3-dihydro-1H-inden-5-yl)pyridin-1(2H)-yl]butanamide 340 (2R)-N-hydroxy-2-methyl-2- 0.0000898 >64.0 0.252 1 0.41 a 432.1 (methylsulfonyl)-4-{4-[4-(1,3-oxazol-5-yl)phenyl]-2-oxopyridin-1(2H)- yl}butanamide 341(2R)-4-[4-(2-chlorophenyl)-2- 0.000431 >64.0 4 4 2 0.48 a 399.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide342 (2R)-4-[4-(2-chloro-4- >0.100 >64.0 0.5 0.5 0.5 0.5 a 429.1methoxyphenyl)-2-oxopyridin-1(2H)- yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 343 (2R)-4-{4-[4-(2-cyano-2- 0.000602 >64.0 816 2 0.51 a 446.2 methylpropyl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 344(2R)-4-{4-[3-fluoro-4-(3- 0.000272 >64.0 4 8 2 0.41 a 441.2hydroxypropyl)phenyl]-2-oxopyridin- 1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 345 (2R)-N-hydroxy-4-[4-(4-methoxy-2-0.000733 >64.0 4 8 4 0.48 a 409.1 methylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 346(2R)-N-hydroxy-4-[4-(4-methoxy-3- 0.0000305 >64.0 0.5 1 0.5 0.51 a 409.1methylphenyl)-2-oxopyridin-1(2H)-yl]- 2-methyl-2-(methylsulfonyl)butanamide 347 (2R)-4-{4-[4-(2-cyanoethyl)phenyl]-2-0.000222 >64.0 64 64 4 0.42 a 418.1 oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 348 (2R)-4-[4-{3-fluoro-4-[(cis-4-0.0000632 >64.0 0.25 4 1 0.49 a 511.2 hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide349 (2R)-4-[4-{3-fluoro-4-[(4-hydroxy-4- 0.000304 >64.0 0.5 16 4 0.47 a511.2 methylcyclohexyl)oxy]phenyl}-2- oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 350(2R)-N-hydroxy-4-{4-[4-(2-hydroxy- 0.00121 >64.0 16 64 16 0.44 a 437.21,1-dimethylethyl)phenyl]-2- oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 351 (2R)-N-hydroxy-4-{4-[4-(1- 0.000572 >64.016 64 16 0.42 a 435.2 hydroxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl)butanamide 352(2R)-N-hydroxy-4-{4-[4-(1- 0.000824 >64.0 2 32 8 0.53 a 449.2methoxycyclobutyl)phenyl]-2- oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 353 (2R)-4-[4-(2,6-difluorophenyl)-2-0.000247 >64.0 4 16 1 0.45 a 401.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 354 (2R)-4-{4-[2-fluoro-4-0.0000764 >64.0 0.25 1 0.5 0.57 a 467.1 (trifluoromethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide355 (2R)-4-[4-{4- 0.000156 >64.0 4 16 2 0.46 a 436.1[(cyanomethyl)thio]phenyl}-2- oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 356(2R)-4-[4-{4-[(cyanomethyl)thio]-2- 0.000324 >64.0 16 32 4 0.49 a 450.1methylphenyl}-2-oxopyridin-1(2H)-yl]- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 357 (2R)-4-[4-{4-[(1- 0.0000515 >64.0 1 16 10.52 a 450.1 cyanoethyl)thio]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 358(2R)-N-hydroxy-2-methyl-2- 0.000166 >64.0 0.25 0.25 1 0.51 a 446.1(methylsulfonyl)-4-{4-[2-methyl-4- (2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide 259 (2R)-N-hydroxy-4-{4-[6-(1-hydroxy-1-0.00199 >64.0 2 32 16 0.48 a 473.2 methylethyl)-2-naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2- (methylsulfonyl)butanamide 360(2R)-N-hydroxy-4-[4-{6-[(1S)-1- 0.0000394 >64.0 0.5 2 1 0.45 a 459.2hydroxyethyl]-2-naphthyl}-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 361 (2R)-4-[4-(4-ethoxy-2-fluorophenyl)-0.000502 >64.0 0.5 2 2 0.54 a 427.1 2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 362 (2R)-4-{4-[4-(1-cyano-1-0.000553 >64.0 16 32 4 0.5 a 432.2 methylethyl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 363(2R)-N-hydroxy-2-methyl-4-{4-[4-(1- 0.00824 >64.0 32 >64.0 64 0.28 a445.2 methyl-1H-imidazol-2-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 364 (2R)-N-hydroxy-2-methyl-2- 0.000394 >64.016 64 16 0.38 a 432.1 (methylsulfonyl)-4-{2-oxo-4-[4-(1H-1,2,3-triazol-1-yl)phenyl]pyridin- 1(2H)-yl}butanamide 365(2R)-4-[4-(4-{[(4R)-4,5- 0.00026 64 4 32 4 0.38 a 483.2dihydroxypentyl]oxy}phenyl)-2- oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 366 (2R)-4-{4-[4-(3,4-0.000566 >64.0 16 >64.0 16 0.35 a 469.2 dihydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide367 (2R)-N-hydroxy-4-{4-[4-(1H-imidazol- 0.00715 >64.0 8 >64.0 >64.00.29 a 431.1 2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 368(2R)-N-hydroxy-2-methyl-4-{4-[4-(2- 0.000343 >64.0 >64.0 >64.0 16 0.29 a445.2 methyl-1H-imidazol-1-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 369 (2R)-N-hydroxy-2-methyl-4-{4-[4-(3- >64.02 8 4 methyl-1H-pyrazol-5-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 370 (2R)-N-hydroxy-2-methyl-4-{4-[4-(5-0.0000595 >64.0 0.125 1 0.5 0.49 a 446.1 methylisoxazol-3-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2- (methylsulfonyl)butanamide 371(2R)-N-hydroxy-2-methyl-2- 0.000207 >64.0 32 32 8 0.37 a 432.1(methylsulfonyl)-4-{2-oxo-4-[4-(1H- 1,2,4-triazol-1-yl)phenyl]pyridin-1(2H)-yl}butanamide 372 (2R)-4-{4-[2-fluoro-4-(2H-1,2,3- 0.0000916 >64.00.06 0.125 2 triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 373(2R)-4-{4-[4-(4,5-dimethyl-2H-1,2,3- 0.0000899 >64.0 0.125 0.5 1 0.55 a460.2 triazol-2-yl)phenyl]-2-oxopyridin- 1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 374 (2R)-N-hydroxy-2-methyl-2- 0.0000573 160.25 0.5 1 0.34 a 442.1 (methylsulfonyl)-4-[2-oxo-4-(4-pyridin-2-ylphenyl)pyridin-1(2H)- yl]butanamide 375(2R)-N-hydroxy-2-methyl-4-{4-[4-(4- 0.000753 >64.0 0.5 2 4 0.48 a 457.2methylpyrimidin-2-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 376 (2R)-N-hydroxy-2-methyl-2- >64.0 0.5 2 2(methylsulfonyl)-4-{4-[4-(2-methyl-2H-tetrazol-5-yl)phenyl]-2-oxopyridin- 1(2H)-yl}butanamide 377(2R)-N-hydroxy-2-methyl-2- 0.0004 32 8 32 8 0.41 a 446.1(methylsulfonyl)-4-{4-[4-(4-methyl- 1H-1,2,3-triazol-1-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide 378 (2R)-N-hydroxy-2-methyl-2-0.00208 >64.0 32 >64.0 64 0.37 a 447.1(methylsulfonyl)-4-{4-[4-(5-methyl-1H-tetrazol-1-yl)phenyl]-2-oxopyridin- 1(2H)-yl}butanamide 379(2R)-N-hydroxy-2-methyl-2- 0.000178 >64.0 0.5 2 2 0.47 a 447.1(methylsulfonyl)-4-{4-[4-(5-methyl-2H-tetrazol-2-yl)phenyl]-2-oxopyridin- 1(2H)-yl}butanamide 380(2R)-N-hydroxy-4-[4-(4-isothiazol-4- 0.00022 >64.0 0.5 4 1 0.49 a 448.1ylphenyl)-2-oxopyridin-1(2H)-yl]-2- methyl-2-(methylsulfonyl)butanamide381 (2R)-N-hydroxy-4-{4-[6-(4- 0.000661 >64.0 1 16 16 0.34 a 514.2hydroxypiperidin-1-yl)-2-naphthyl]-2- oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 382 (2R)-4-{4-[4-(3,5-dimethyl-4H-1,2,4-0.0398 >64.0 >64.0 >64.0 >64.0 0.3 a 460.2triazol-4-yl)phenyl]-2-oxopyridin- 1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 383 (2R)-N-hydroxy-2-methyl-2-0.00385 >64.0 >64.0 >64.0 >64.0 0.3 a 446.1(methylsulfonyl)-4-{4-[4-(3-methyl- 4H-1,2,4-triazol-4-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide 384 (2R)-4-{4-[4-(3,5-dimethyl-1H-1,2,4-0.00159 >64.0 8 64 16 0.35 a 460.2 triazol-1-yl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 385(2R)-4-[4-(2-ethoxyquinolin-6-yl)-2- 0.0000468 4 0.06 0.5 0.5 0.55 a460.2 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 386(2R)-4-[4-(2,4-dichlorophenyl)-2- >64.0 2 2 2oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide387 (2R)-N-hydroxy-4-{4-[4-(5- 0.0000131 >64.0 0.06 0.5 0.5 0.49 a 473.1methoxypyrimidin-2-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 388(2R)-N-hydroxy-4-{4-[4-(1H-imidazol- >0.00533 >64.0 16 >64.0 16 0.28 a431.1 1-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 389 (2R)-N-hydroxy-2-methyl-2-0.000187 >64.0 1 2 1 0.44 a 432.1 (methylsulfonyl)-4-{4-[4-(1,3-oxazol-4-yl)phenyl]-2-oxopyridin-1(2H)- yl}butanamide 390(2R)-N-hydroxy-4-[4-(4- 0.000485 >64.0 0.25 0.5 0.5 0.56 a 423.2isopropoxyphenyl)-2-oxopyridin- 1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 391 (2R)-N-hydroxy-2-methyl-2- 0.000378 >64.00.25 1 0.5 0.58 a 449.1 (methylsulfonyl)-4-{2-oxo-4-[4-(trifluoromethoxy)phenyl]pyridin- 1(2H)-yl}butanamide 392(2R)-4-[4-(2-chloro-5-fluorophenyl)-2- 0.00587 >64.0 16 16 8 0.51 a417.1 oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 393 (2R)-4-[4-(2-fluoro-4- 0.00021464 0.5 1 1 0.53 a 427.1 methoxyphenyl)-3-methyl-2-oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide394 (2R)-4-[4-(4-chloro-2-fluorophenyl)-3- 0.000248 >64.0 1 1 1 0.59 a431.1 methyl-2-oxopyridin-1(2H)-yl]-N- hydroxy-2-methyl-2-(methylsulfonyl)butanamide 395 (2R)-4-[4-(4-fluorophenyl)-3-methyl-0.000325 >64.0 1 4 2 0.53 a 397.1 2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 396(2R)-4-[4-(4-chlorophenyl)-3-methyl- 0.000107 >64.0 0.25 0.5 0.5 0.58 a413.1 2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 397 (2R)-N-hydroxy-4-[4-(4- 0.00012564 0.25 0.5 1 0.51 a 409.1 methoxyphenyl)-3-methyl-2-oxopyridin-1(2H)-yl]-2-methyl-2- (methylsulfonyl)butanamide 398(2R)-4-[4-(4-cyanophenyl)-3-methyl- 0.000349 64 4 8 2 0.46 a 404.12-oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide399 (2R)-4-{4-[4- 0.000119 64 0.5 1 1 0.55 a 445.1(difluoromethoxy)phenyl]-3-methyl-2- oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 400 (2R)-N-hydroxy-2-methyl-2-0.000338 >64.0 1 4 2 0.4 a 443.1 (methylsulfonyl)-4-[2-oxo-4-(4-pyrimidin-4-ylphenyl)pyridin-1(2H)- yl]butanamide 401(2R)-N-hydroxy-2-methyl-2- 0.00146 >64.0 8 16 8 0.35 a 448.1(methylsulfonyl)-4-{4-[4-(1-oxido-2H- 1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide 402 (2R)-N-hydroxy-2-methyl-2-0.000272 >64.0 0.5 2 2 0.3 a 442.1 (methylsulfonyl)-4-[2-oxo-4-(4-pyridin-4-ylphenyl)pyridin-1(2H)- yl]butanamide 403(2R)-N-hydroxy-4-[4-{4-[2-(2- 0.000582 64 1 8 4 0.45 a 483.2methoxyethoxy)ethoxy]phenyl}-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 404 (2R)-4-[4-(2-ethoxypyrimidin-5-yl)-2-0.0507 >64.0 >64.0 >64.0 >64.0 0.38 a 411.1oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide405 (2R)-N-hydroxy-2-methyl-2- 0.000194 >64.0 0.125 0.25 1 0.47 a 448.1(methylsulfonyl)-4-{2-oxo-4-[4-(1,3- thiazol-4-yl)phenyl]pyridin-1(2H)-yl}butanamide 406 (2R)-N-hydroxy-2-methyl-2- 0.000153 >64.0 0.25 1 0.50.44 a 448.1 (methylsulfonyl)-4-{2-oxo-4-[4-(1,3-thiazol-5-yl)phenyl]pyridin-1(2H)- yl}butanamide 407(2R)-N-hydroxy-4-{4-[4-(4-hydroxy- 0.00263 64 16 64 32 0.41 a 448.12H-1,2,3-triazol-2-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 408 (2R)-N-hydroxy-4-[4-{4-[3- 0.000657 >64.08 16 8 0.39 a 462.1 (hydroxymethyl)isoxazol-5-yl]phenyl}-2-oxopyridin-1(2H)-yl]-2- methyl-2-(methylsulfonyl)butanamide409 (2R)-4-[4-{4-[2- 0.000196 >64.0 0.5 2 2 0.45 a 486.2(dimethylamino)pyrimidin-5- yl]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 410(2R)-N-hydroxy-4-{4-[4-(2- 0.00015 >64.0 0.5 2 1 0.45 a 473.2methoxypyrimidin-5-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 411 (2R)-N-hydroxy-4-[4-(4-isoxazol-5-0.000165 >64.0 0.5 1 0.5 0.45 a 432.1ylphenyl)-2-oxopyridin-1(2H)-yl]-2- methyl-2-(methylsulfonyl)butanamide412 (2R)-4-[4-(4-cyano-2-fluorophenyl)-3- 0.00127 >64.0 8 16 4 0.47 a422.1 methyl-2-oxopyridin-1(2H)-yl]-N- hydroxy-2-methyl-2-(methylsulfonyl)butanamide 413 (2R)-4-[4-(3-chloro-2-fluorophenyl)-3-0.00125 >64.0 2 2 2 0.56 a 431.1 methyl-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 414(2R)-4-[4-(2,3-dichlorophenyl)-3- 0.00192 >64.0 2 4 8 0.58 a 447.1methyl-2-oxopyridin-1(2H)-yl]-N- hydroxy-2-methyl-2-(methylsulfonyl)butanamide 415 (2R)-4-{4-[4-(6-cyanopyridin-3- >64.0 1 42 yl)phenyl]-2-oxopyridin-1(2H)-yl}-N- hydroxy-2-methyl-2-(methylsulfonyl)butanamide 416 (2R)-4-{4-[4-(4,5-dimethyl-1H-1,2,3-0.00194 >64.0 64 >64.0 32 0.42 a 460.2triazol-1-yl)phenyl]-2-oxopyridin- 1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 417 (2R)-N-hydroxy-2-methyl-2- 0.0151 >64.08 >64.0 64 0.36 a 433.1 (methylsulfonyl)-4-{4-[4-(1,2,4-oxadiazol-5-yl)phenyl]-2-oxopyridin- 1(2H)-yl}butanamide 418(2R)-N-hydroxy-4-[6- >0.100 >64.0 >64.0 >64.0 64 0.21 a 396.1(hydroxymethyl)-2′-oxo-3,4′-bipyridin- 1′(2′H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 419 (2R)-N-hydroxy-2-methyl-2- 0.000127 >64.00.25 1 1 0.46 a 449.1 (methylsulfonyl)-4-{2-oxo-4-[4-(1,2,4-thiadiazol-5-yl)phenyl]pyridin-1(2H)- yl}butanamide 420(2R)-N-hydroxy-2-methyl-4-[1′-(5- 0.00172 >64.0 4 8 8 0.39 a 462.2methylpyrimidin-2-yl)-2-oxo- 1′,2′,3′,6′-tetrahydro-4,4′-bipyridin-1(2H)-yl]-2- (methylsulfonyl)butanamide 421 (2R)-N-hydroxy-2-methyl-2-0.000911 >64.0 >64.0 >64.0 64 0.37 a 433.1(methylsulfonyl)-4-{2-oxo-4-[4-(1H- tetrazol-1-yl)phenyl]pyridin-1(2H)-yl}butanamide 422 (2R)-N-hydroxy-2-methyl-4-{4-[4-(6- 0.0012 >64.0 0.5 24 0.33 a 456.2 methylpyridin-2-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 423 (2R)-N-hydroxy-2-methyl-2- >64.0 1 8 4(methylsulfonyl)-4-[2-oxo-4-(4- pyrimidin-5-ylphenyl)pyridin-1(2H)-yl]butanamide 424 (2R)-N-hydroxy-2-methyl-2- 0.000708 >64.0 4 8 4 0.41 a459.1 (methylsulfonyl)-4-{2-oxo-4-[4- (pyrimidin-2-yloxy)phenyl]pyridin-1(2H)-yl}butanamide 425 (2R)-N-hydroxy-2-methyl-2- <0.00100 0.55 a 501.2(methylsulfonyl)-4-[2-oxo-4-{4-[(5- propylpyrimidin-2-yl)oxy]phenyl}pyridin-1(2H)- yl]butanamide 426 (2R)-4-{4-[4-(2- 0.00019332 0.25 1 1 0.56 a 482.1 cyanophenoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 427(2R)-4-[4-{4-[(3-cyanopyridin-2- <0.00100 >64.0 2 4 2 0.5 a 483.1yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 428 (2R)-4-[4-{4-[(4-chloropyridin-2-0.000235 >64.0 0.125 0.5 1 0.54 a 492.1yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 429 (2R)-N-hydroxy-2-methyl-2- <0.00100 0.44a 459.1 (methylsulfonyl)-4-{2-oxo-4-[4- (pyrazin-2-yloxy)phenyl]pyridin-1(2H)-yl}butanamide 430 (2R)-4-[4-{4-[(5-chloropyridin-2- 0.000305 640.125 0.5 2 0.59 a 492.1 yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 431(2R)-4-[4-{4-[(3-cyano-4- 0.000444 0.54 a 497.1methylpyridin-2-yl)oxy]phenyl}-2- oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 432(2R)-N-hydroxy-2-methyl-4-[4-{4-[(4- <0.00100 0.51 a 472.2methylpyridin-2-yl)oxy]phenyl}-2- oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide 433 (2R)-4-{4-[4-(6,7-dihydro-5H- 0.47 a499.2 cyclopenta[d]pyrimidin-4- yloxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 434(2R)-4-[4-{4-[(5-chloropyrimidin-2- <0.00100 0.51 a 493.1yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 435 (2R)-N-hydroxy-2-methyl-4-[4-{4-[(3-<0.00100 0.48 a 473.1 methylpyrazin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2- (methylsulfonyl)butanamide 436(2R)-N-hydroxy-2-methyl-2- No >64.0 0.5 1 2 0.54 a 458.1(methylsulfonyl)-4-{2-oxo-4-[4- Summarized(pyridin-2-yloxy)phenyl]pyridin-1(2H)- Data yl}butanamide 437(2R)-4-{4-[4-(furo[3,2-c]pyridin-4- 0.000683 >64.0 0.25 0.5 4 0.54 a498.1 yloxy)phenyl]-2-oxopyridin-1(2H)-yl}- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 438 (2R)-4-[4-{4-[(3-cyano-6- 0.000998 >64.04 16 8 0.54 a 497.1 methylpyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide439 (2R)-N-hydroxy-4-[4-{4-[(1-isopropyl- 0.00105 0.5 a 491.21H-tetrazol-5-yl)oxy]phenyl}-2- oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 440 (2R)-4-[4-{4-[(3-chloropyridin-2-0.000325 64 0.06 0.5 2 0.58 a 492.1yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 441 (2R)-4-[4-{4-[(3-cyano-4,6- <0.00100 0.57a 511.2 dimethylpyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide442 (2R)-4-[4-{4-[(2-cyanopyridin-3- 0.000188 >64.0 4 16 4 0.49 a 483.1yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 443 (2R)-N-hydroxy-2-methyl-4-[4-{4-[(5-<0.00316 0.45 a 473.1 methylpyrimidin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2- (methylsulfonyl)butanamide 444(2R)-N-hydroxy-2-methyl-2- 0.000259 >64.0 0.125 1 2 a(methylsulfonyl)-4-{2-oxo-4-[4- (quinolin-4-yloxy)phenyl]pyridin-1(2H)-yl}butanamide 445 (2R)-4-{4-[4-(1,3-benzothiazol-2- 0.000245 >64.00.25 2 4 a yloxy)phenyl]-2-oxopyridin-1(2H)-yl}- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 446 (2R)-4-[4-{4-[(3-cyano-4- 0.000374 0.51 a513.1 methoxypyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide447 (2R)-N-hydroxy-2-methyl-4-[4-{4-[(2- 0.000358 0.35 a 472.1methylpyridin-4-yl)oxy]phenyl}-2- oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide 448 (2R)-4-[4-{4-[(5-fluoropyrimidin-2-0.000208 0.46 a 477.1 yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 449(2R)-4-[4-{4-[(4,6-dimethylpyrimidin- 0.00109 0.48 a 487.22-yl)oxy]phenyl}-2-oxopyridin-1(2H)- yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 450 (2R)-4-{4-[4-(1,2-benzisoxazol-3-0.000247 32 0.06 0.5 2 0.61 a 498.1yloxy)phenyl]-2-oxopyridin-1(2H)-yl}- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 451 (2R)-4-[4-(2,3-dichloro-5- 0.00139 64 4 44 0.57 a 451 fluorophenyl)-2-oxopyridin-1(2H)-yl]- N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 452 (2R)-4-[4-(2,3-dichloro-4- 0.000996 >64.04 4 2 0.55 a 463 methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 453(2R)-N-hydroxy-2-methyl-2- 0.00195 >64.0 4 64 8 0.36 a 443.1(methylsulfonyl)-4-[2-oxo-4-(4- pyridazin-3-ylphenyl)pyridin-1(2H)-yl]butanamide 454 (2R)-N-hydroxy-4-[4-(4-isoxazol-4- 0.00332 >64.0 2 164 0.45 a 432.1 ylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 455 (2R)-N-hydroxy-2-methyl-2-0.000169 >64.0 0.06 0.125 1 a (methylsulfonyl)-4-{4-[4-(4-methyl-2H-1,2,3-triazol-2-yl)phenyl]-2- oxopyridin-1(2H)-yl}butanamide 456(2R)-N-hydroxy-2-methyl-4-{4-[4-(6- 0.000205 >64.0 0.25 1 1 0.32 a 456.2methylpyridin-3-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 457 (2R)-N-hydroxy-2-methyl-4-{4-[4-(5-0.00104 >64.0 0.5 2 2 0.46 a 457.2 methylpyrazin-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2- (methylsulfonyl)butanamide 458(2R)-4-{4-[4-(5-chloropyrimidin-2- 0.000155 >64.0 0.06 0.5 0.5 0.57 a477 yl)phenyl]-2-oxopyridin-1(2H)-yl}-N- hydroxy-2-methyl-2-(methylsulfonyl)butanamide 459 (2R)-4-[4-(3,5-difluoro-4- >64.0 2 8 2methoxyphenyl)-2-oxopyridin-1(2H)- yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 460 (2S)-4-[4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)- yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 461 (2R)-N-hydroxy-2-methyl-4-{4-[4-(5- >64.00.125 1 1 methylpyrimidin-2-yl)phenyl]-2- oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide 462 (2R)-N-hydroxy-2-methyl-2- >64.0 0.5 1 1(methylsulfonyl)-4-{2-oxo-4-[4- (tetrahydrofuran-2-ylmethoxy)phenyl]pyridin-1(2H)- yl}butanamide 463trans-4-[(4-{1-[(3R)-4- (hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo- 1,2-dihydropyridin-4-yl}phenoxy)methyl]cyclohexyl dihydrogen phosphate 464(2R)-4-[4-(4-butylphenyl)-2- 0.000166 8 0.03 0.25 1 0.67 a 421.2oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide465 (2R)-N-hydroxy-2-methyl-2- 0.000189 64 0.125 0.5 0.5 0.62 a 407.2(methylsulfonyl)-4-[2-oxo-4-(4- propylphenyl)pyridin-1(2H)-yl]butanamide 466 (2R)-N-hydroxy-4-[4-(3- 64 2 16 4isopropylphenyl)-2-oxopyridin-1(2H)- yl]-2-methyl-2-(methylsulfonyl)butanamide 467 (2R)-4-[4-(4-cyano-3-methylphenyl)-0.0000999 >64.0 4 8 2 2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 468(2R)-N-hydroxy-4-[4-(3-methoxy-2- >64.0 2 4 2methylphenyl)-2-oxopyridin-1(2H)-yl]- 2-methyl-2-(methylsulfonyl)butanamide 469 (2R)-N-hydroxy-2-methyl-2- 0.0205(methylsulfonyl)-4-[2-oxo-4-(1- phenyl-1H-pyrazol-4-yl)pyridin-1(2H)-yl]butanamide 470 (2R)-N-hydroxy-4-{4-[3-(2- 0.0016 >64.0 16 32 32methoxyethyl)phenyl]-2-oxopyridin- 1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide 471 (2R)-N-hydroxy-2-methyl-2- 0.00323(methylsulfonyl)-4-[2-oxo-4-(5- phenyl-1,3,4-thiadiazol-2-yl)pyridin-1(2H)-yl]butanamide 472 (2R)-4-[4-(4-cyano-2-methylphenyl)- >64.0 32 648 2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 473(2R)-4-[4-(3-aminoisoquinolin-7-yl)-2- >64.0 16 64 16oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide474 (2R)-N-hydroxy-2-methyl-2- 0.00895 >64.0 64 >64.0 64(methylsulfonyl)-4-[2-oxo-4-(2- phenyl-1,3-oxazol-5-yl)pyridin-1(2H)-yl]butanamide 475 (2R)-4-[4-{3-[(1- >64.0 8 32 8cyanoethyl)thio]phenyl}-2-oxopyridin- 1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 476 (2R)-4-[4-(3-cyano-4-methylphenyl)-0.000932 >64.0 16 64 8 2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 477 (2R)-4-[4-(4-cyano-2-fluoro-5-0.00192 >64.0 64 >64.0 32 methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 478 methyl3-(4-{1-[(3R)-4- 0.000129 >64.0 2 4 1 (hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo- 1,2-dihydropyridin-4-yl}phenyl)propanoate 479 (2R)-4-[4-(3-cyano-4-ethoxyphenyl)-0.00461 >64.0 64 >64.0 16 2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 480 (2R)-4-{4-[3- 0.00202 >64.0 8 164 (difluoromethoxy)phenyl]-2- oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide 481 (2R)-N-hydroxy-2-methyl-2-0.0236 >64.0 >64.0 >64.0 64 (methylsulfonyl)-4-[2-oxo-4-(1-oxo-3,4-dihydro-1H-isochromen-7- yl)pyridin-1(2H)-yl]butanamide 482(2R)-N-hydroxy-4-[4-(4- 0.0213 >64.0 >64.0 >64.0 >64.0methoxyquinolin-6-yl)-2-oxopyridin- 1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide 483 (2R)-N-hydroxy-2-methyl-4-[4-(3-0.000808 >64.0 8 32 8 methyl-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-2-oxopyridin- 1(2H)-yl]-2- (methylsulfonyl)butanamide484 (2R)-N-hydroxy-2-methyl-4-[4-(4- >64.0 >64.0 >64.0 >64.0methyl-2-oxo-1,2,3,4- tetrahydroquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-2- (methylsulfonyl)butanamide 485(2R)-4-[4-(3-aminoisoquinolin-6-yl)-2- 0.00129 >64.0 64 >64.0 32oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide486 (2R)-N-hydroxy-2-methyl-2- 0.0304 >64.0 >64.0 >64.0 >64.0(methylsulfonyl)-4-[2-oxo-4-(3-oxo- 1,3-dihydro-2-benzofuran-5-yl)pyridin-1(2H)-yl]butanamide 487 (2R)-4-{4-[4-(difluoromethoxy)-2,3-0.000178 0.59 a 467.3 difluorophenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2- (methylsulfonyl)butanamide 4884-[4-(3-cyclopentylpropoxy)-2- 0.0109 64 8 64 64 0.71 a 415.2oxopyridin-1(2H)-yl]-N-hydroxy-2- methyl-2-(methylsulfonyl)butanamide

What is claimed is:
 1. A compound selected from the group consisting of:(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1H-pyrazol-1-yl)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[(E)-2-phenylvinyl]pyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2-phenylethyl)pyridin-1(2H)-yl]butanamide;4-[4-{4-[3-(4,4-difluoropiperidin-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[4-(cis-3-hydroxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(3-hydroxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[(4-hydroxycyclohexyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[(cis-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{2-fluoro-4-[(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[(4-hydroxy-4-methylcyclohexyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[(3-hydroxy-3-methylcyclobutyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(3-cyanopropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-(4-{[3-(hydroxymethyl)cyclobutyl]methoxy}phenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-{4-[(4hydroxy-4-methylpentyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(4-{[3-(hydroxymethyl)cyclobutyl]oxy}phenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(3-hydroxypropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(3-hydroxypropyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[2-(3-hydroxycyclobutyl)ethoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(1-benzofuran-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(6-methoxy-2-naphthyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyridin-4-ylphenyl)pyridin-1(2H)-yl]butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-quinolin-7-ylpyridin-1(2H)-yl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2-pyridin-4-ylethoxy)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-4-{4-[4-(5-methyl-1,3-oxazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyrimidin-2-ylphenyl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-4-[4-(4-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2,3-difluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2,3-dichlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(tetrahydro-2H-pyran-4-yl)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-4-[4-{4-[(2-methoxyethyl)thio]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2,3,4-trifluorophenyl)pyridin-1(2H)-yl]butanamide;4-[4-(benzyloxy)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-(3-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanamide;4-(4-cyclohexyl-2-oxopyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;2-ethyl-N-hydroxy-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanamide;(2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-(5-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;2-(ethylsulfonyl)-N-hydroxy-2-methyl-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanamide;(2R)-N-hydroxy-4-{4-[4-(4-methoxy-2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-(4-{[(6-methoxypyridin-3-yl)oxy]methyl}phenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4[difluoro(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[4-(hydroxymethyl)piperidin-1-yl]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-{4-[(1E)-N-methoxyethanimidoyl]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-{4-[3-(hydroxymethyl)isoxazol-5-yl]-3-methylphenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(3-phenylazetidin-1-yl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(phenylethynyl)pyridin-1(2H)-yl]butanamide;4-[4-(3-cyclohexylpropoxy)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-1′-pyrimidin-2-yl-1′,2′,3′,6′-tetrahydro-4,4′-bipyridin-1(2H)-yl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[4-(2-naphthyl)-2-oxopyridin-1(2H)-yl]butanamide;(2R)-4-[4-(4-chloro-3-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3,4-dichlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1,3-thiazol-2-yl)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-4-[4-(2-chloro-3-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-(4-isoxazol-3-ylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-propionylphenyl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-4-{4-[4-(cis-3-hydroxy-3-methylcyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(trifluoromethyl)phenyl]pyridine-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-4-{3-methyl-2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;(2R)-4-(4-cyclohex-1-en-1-yl-2-oxopyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-(4-cyclohept-1-en-1-yl-2-oxopyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[(3-hydroxycyclobutyl)methyl]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{6-[(1S)-1-hydroxyethyl]-2-naphthyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(6-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4[2-oxo-4-(5-phenyl-2-thienyl)pyridin-1(2H)-yl]butanamide;N-hydroxy-4-{4[4-(1-hydroxyethyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4[4-(1-methyl-1H-indol-2-yl)-2-oxopyridin-1(2H)-yl]-2-methylsulfonyl)butanamide;4-[4-(2-cyclopentylethoxy)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-(4-cyclohex-1-en-1-yl-2-oxopyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2-phenylethoxy)pyridin-1(2H)-yl]butanamide;4-[4-(4-acetylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[4-(1,1-difluoro-2-hydroxyethyl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-fluoro-4-hydroxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(3-morpholin-4-ylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;N-hydroxy-4-{4-[4-(hydroxymethyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-glycoloylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4[4-(2-pyrrolidin-1-ylethoxy)phenyl]pyridin-1(2H)-yl}butanamide;N-hydroxy-4-{4-[4-(4-hydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[3-fluoro-4-(2-hydroxyethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(3-piperidin-1-ylpropoxy)phenyl]pyridin-1(2H)-yl}butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]pyridin-1(2H)-yl}butanamide;N-hydroxy-4-[4-(1H-indol-5-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-{4-[(1E)-N-hydroxyethanimidoyl]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(3-thiomorpholin-4-ylpropoxy)phenyl]pyridin-1(2H)-yl}butanamide;4-[4-{4-[3-(1,1-dioxidothiomorpholin-4-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-{4-[3-(4-hydroxypiperidin-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-{4-[3-(3-hydroxyazetidin-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-{4-[3-(3-oxopiperazin-1-yl)propoxy]phenyl}pyridin-1(2H)-yl]butanamide;N-hydroxy-2-methyl-4-[4-{4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(3-pyridin-3-ylpropoxy)phenyl]pyridin-1(2H)-yl}butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(3-pyridin-4-ylpropoxy)phenyl]pyridin-1(2H)-yl}butanamide;4-[4-(2-fluoro-3-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(1H-indol-2-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-{4-[3-(1H-1,2,4-triazol-1-yl)propoxy]phenyl}pyridin-1(2H)-yl]butanamide;4-[4-{4-[3-(3,3-difluoropyrrolidin-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(2-morpholin-4-ylethoxy)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;N-hydroxy-4-[4-{4-[3-(hydroxymethyl)isoxazol-5-yl]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(2-fluoro-3-hydroxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(4-hydroxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanamide;4-[4-(4-acetyl-3-hydroxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-{4-[3-(3,3-difluoropiperidin-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[4-(4-nitrophenyl)-2-oxopyridin-1(2H)-yl]butanamide;N-hydroxy-2-methyl-4-[4-{4-[(methylamino)sulfonyl]phenyl}-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;N-ethyl-3-fluoro-5-{1-[4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}benzamide;N-hydroxy-2-methyl-4-{4-[4-(1-methyl-1H-imidazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;4-[4-(5-chloro-2-ethoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-{4-[(dimethylamino)sulfonyl]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(3-thienyl)pyridin-1(2H)-yl]butanamide;4-[4-(5-amino-2-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-(4-isoquinolin-4-yl-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-aminophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[3-(1H-pyrazol-1-yl)phenyl]pyridin-1(2H)-yl}butanamide;4-[4-(3-fluoro-5-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{1-[4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}-3-methylbenzamide;4-[4-(3-chlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-amino-4-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[6-(dimethylamino)-2′-oxo-3,4′-bipyridin-1′(2′H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(5-fluoro-2-hydroxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-furyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-cyclohexylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(2-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-chloro-5-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-fluoro-2-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(2,3-difluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-quinolin-3-ylpyridin-1(2H)-yl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-quinolin-3-ylpyridin-1(2H)-yl)butanamide;N,N-diethyl-4-{1-[4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}benzamide;4-[4-(3-acetylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(7-chlorothieno[3,2-b]pyridin-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[4-(cyanomethyl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(3,4,5-trifluorophenyl)pyridin-1(2H)-yl]butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[2-(2,2,2-trifluoroethoxy)phenyl]pyridin-1(2H)-yl}butanamide;4-[4-(2-cyanophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-acetamidophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3,4-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-chloro-3-cyanophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[4-(ethylsulfonyl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[5-fluoro-2-(trifluoromethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3,4-dimethoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(4-methoxyphenoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(2-acetylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-chlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-chloro-3-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[3-(trifluoromethyl)phenyl]pyridin-1(2H)-yl}butanamide;N-hydroxy-4-{4-[3-(hydroxymethyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(trifluoromethoxy)phenyl]pyridin-1(2H)-yl}butanamide;4-{1-[4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}-N-isopropylbenzamide;4-[4-(2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-{3-[(dimethylamino)sulfonyl]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(5-cyano-2-thienyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(5-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-fluoro-4-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(1-propyl-1H-pyrazol-4-yl)pyridin-1(2H)-yl]butanamide;4-[4-(3-fluoro-2-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-tert-butyl-1′-[4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2′-oxo-1′,2′-dihydro-3,4′-bipyridine-5-carboxamide;4-[4-(2-chloro-4-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-phenoxyphenyl)pyridin-1(2H)-yl]butanamide;4-[4-(2-chloro-3-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-[4-(5-methyl-2-furyl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;4-[4-(2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-{5-[(dimethylamino)sulfonyl]-2-methylphenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(2,4-dimethoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-[4-(2-methyl-3-oxo-2,3-dihydro-1H-isoindol-5-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;4-[4-(2,3-dichlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(2,3-dihydro-1-benzofuran-5-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(1-benzyl-1H-pyrazol-4-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-fluoro-2-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(5-acetyl-2-thienyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-(2-isopropoxy-2′-oxo-3,4′-bipyridin-1′(2′H)-yl)-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-cyanophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(5-fluoro-2-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-{4-[3-(1-methyl-1H-imidazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;4-[4-(5-fluoro-2-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2,4-bis(trifluoromethyl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(2-furyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(1H-indol-6-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-ethyl-2-fluoro-4-{1-[4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}benzamide;N-hydroxy-2-methyl-4-[4-(3-methylphenyl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-[4-(2-methyl-1-oxo-2,3-dihydro-1H-isoindol-5-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;4-[4-(3-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[6-(cyclohexylmethoxy)-2′-oxo-3,4′-bipyridin-1′(2′H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-(2-methoxy-2′-oxo-3,4′-bipyridin-1′(2′H)-yl)-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[2-(trifluoromethyl)phenyl]pyridin-1(2H)-yl}butanamide;4-[4-(4-ethoxy-3-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-(6-ethoxy-2′-oxo-3,4′-bipyridin-1′(2′H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(2,4-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{1-[4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}-N-methylbenzamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-quinolin-8-ylpyridin-1(2H)-yl)butanamide;N-hydroxy-2-methyl-4-[4-(4-methylphenyl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[2-(methoxymethyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-fluoro-3-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(2,5-dimethoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(2,5-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(2-fluorobiphenyl-4-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-cyanophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-butylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-(6-methoxy-2-methyl-2′-oxo-3,4′-bipyridin-1′(2′H)-yl)-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-[4-(2-methylphenyl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;3-fluoro-5-{1-[4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}-N-methylbenzamide;N-hydroxy-2-methyl-4-[4-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;4-[4-(2-chloro-5-hydroxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-(2-ethoxy-2′-oxo-3,4′-bipyridin-1′(2′H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(3-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-cyano-3-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-fluoro-3-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-(2′-methyl-2-oxo-4,4′-bipyridin-1(2H)-yl)-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(3-hydroxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-tert-butyl-2-fluoro-5-{1-[4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}benzamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(3,4,5-trimethoxyphenyl)pyridin-1(2H)-yl]butanamide;N-hydroxy-4-[4-(2-hydroxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-chloro-4-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-methylsulfonyl)butanamide;N-hydroxy-4-(4-isoquinolin-5-yl-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3,5-dichlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pentylphenyl)pyridin-1(2H)-yl]butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4,4′-bipyridin-1(2H)-yl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2′-oxo-3,4′-bipyridin-1′(2′H)-yl)butanamide;N-hydroxy-2-methyl-4-(6-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanamide;4-{4-[3-chloro-4-(3-morpholin-4-ylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-{4-[3-methyl-4-(3-morpholin-4-ylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;4-{4-[3-fluoro-4-(3-morpholin-4-ylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(2-hydroxypropyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2-chloro-4-(3-morpholin-4-ylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2-fluoro-4-(3-morpholin-4-ylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[3-methoxy-4-(3-morpholin-4-ylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-{4-[2-methyl-4-(3-morpholin-4-ylpropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-{4-[(5-hydroxypentyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[4-(aminosulfonyl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[3-(2-hydroxypropyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2-chloro-4-(2-hydroxyethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(2-hydroxyethoxy)-2,5-dimethylphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2,3-dichloro-4-(2-hydroxyethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(2-hydroxyethoxy)-3-methylphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[3-chloro-4-(2-hydroxyethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(2-hydroxyethoxy)-2-methylphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[3-chloro-4-(4-hydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2-chloro-4-(4-hydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[3-fluoro-4-(4-hydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2-fluoro-4-(4-hydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(4-hydroxybutoxy)-3-methoxyphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(4-hydroxybutoxy)-2-methylphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2,5-dichloro-4-(2-hydroxyethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(4-hydroxybutoxy)-2-methoxyphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[3-chloro-4-(3-hydroxypropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[3-fluoro-4-(3-hydroxypropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(3-hydroxypropoxy)-3-methylphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(3-hydroxypropoxy)-3-methoxyphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2-fluoro-4-(3-hydroxypropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2-chloro-4-(3-hydroxypropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(3-hydroxypropoxy)-2-methylphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[4-(3-hydroxypropoxy)-2-methoxyphenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-quinolin-6-ylpyridin-1(2H)-yl)butanamide;N-hydroxy-4-{4-[4-(2-hydroxy-2-methylpropyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-[4-(2-methyl-1H-indol-5-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;4-[4-(2,3-dimethylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(6-hydroxy-2-naphthyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyridin-2-ylphenyl)pyridin-1(2H)-yl]butanamide;N-hydroxy-4-(4-isoquinolin-6-yl-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-(4-isoquinolin-7-yl-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[3-(2-hydroxy-2-methylpropyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[3-(2-hydroxyethyl)-1H-indol-5-yl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(2-fluoro-3-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[1-(2-hydroxyethyl)-1H-indol-5-yl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-chloro-2-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[1-(3-hydroxypropyl)-1H-indol-5-yl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-4-ylmethoxy)phenyl]pyridin-1(2H)-yl}butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-3-ylmethoxy)phenyl]pyridin-1(2H)-yl}butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-2-ylmethoxy)phenyl]pyridin-1(2H)-yl}butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2-pyridin-3-ylethoxy)phenyl]pyridin-1(2H)-yl}butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2-pyridin-2-ylethoxy)phenyl]pyridin-1(2H)-yl}butanamide;N-hydroxy-4-{4-[6-(2-hydroxyethoxy)-2-naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[6-(3-hydroxypropoxy)-2-naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(1H-indazol-5-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;4-[4-{4-[4-(aminosulfonyl)butoxy]-2-chlorophenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[4-{4-[(5-morpholin-4-ylpentyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]butanamide;4-{4-[4′-(aminosulfonyl)biphenyl-4-yl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[4-(4-hydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[(5-hydroxypentyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;4-[6-(4-fluorophenyl)-2′-oxo-3,4′-bipyridin-1′(2′H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-bromo-3-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(4-bromo-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-(5-methyl-2-oxo-4-phenylpyridin-1(2H)-yl)-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-(6-methoxy-2′-oxo-3,4′-bipyridin-1′(2′H)-yl)-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-{4[3-(hydroxymethyl)isoxazol-5-yl]-2-methylphenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-3-yloxy)phenyl]pyridin-1(2H)-yl}butanamide;N-hydroxy-4-[4-(7-methoxy-2-naphthyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[4-{2-methyl-4-[3-(1H-1,2,4-triazol-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]butanamide;4-[4-{3-chloro-4-[3-(1H-1,2,4-triazol-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-{2-chloro-4-[3-(1H-1,2,4-triazol-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-{2,3-dichloro-4-[3-(1H-1,2,4-triazol-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[4-{3-methyl-4-[3-(1H-1,2,4-triazol-1-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]butanamide;N-hydroxy-2-(methylsulfonyl)-2[2-(2-oxo-4-phenylpyridin-1(2H)-yl)ethyl]pentanamide;4-[4-(2-fluoro-4-pyridin-3-ylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(1H-indol-3-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-fluoro-4-pyridin-3-ylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-[4-(3-fluoro-4-pyridin-4-ylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-4-[4-(7-hydroxy-2-naphthyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-[4-(2-methylquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-[4-(3-methylquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-[4-(4-methylquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;(2R)-4-[4-{2,3-dichloro-4-[2-(4-hydroxypiperidin-1-yl)ethoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[2,3-dichloro-4-(2-morpholin-4-ylethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-[4-(2-methylquinolin-7-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;4-[4-(7-fluoroisoquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;4-{4-[2-fluoro-3-(3-hydroxypropoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;N-hydroxy-2-methyl-4-[4-(3-methylquinolin-7-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;N-hydroxy-4-{4-[6-(hydroxymethyl)-2-naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[4-(6-methoxypyridin-3-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(1-glycoloylpiperidin-4-yl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[2-(1-glycoloylpiperidin-4-yl)ethoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[3-(1-glycoloylpiperidin-4-yl)propoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[6-(2-hydroxyethoxy)-2-naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[6-(hydroxymethyl)-2-naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3-fluoroquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{3-fluoro-4-[(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[(4-hydroxybutyl)thio]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-acetyl-2-fluorophenyl)-2-oxopyridin-1(2H)yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2,4-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3-fluoro-4-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2-fluoro-3-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4[2-fluoro-4-(4-hydroxybutoxy)-3-methylphenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-fluoro-3-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{2-fluoro-4-[(4-hydroxy-4-methylcyclohexyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2-oxo-1,2-dihydroquinolin-6-yl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-4-[4-(2-methoxyquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[4-(4-hydroxypiperidin-1-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2′-oxo-6-(trifluoromethyl)-3,4′-bipyridin-1(2′H)-yl]butanamide;(2R)-4-[4-(4-ethoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(cyanomethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3-chloro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3,5-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3,5-dichlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[3-fluoro-4-(piperidin-4-yloxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(difluoromethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(1-oxo-2,3-dihydro-1H-inden-5-yl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(1,3-oxazol-5-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;(2R)-4-[4-(2-chlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2-chloro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(2-cyano-2-methylpropyl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[3-fluoro-4-(3-hydroxypropyl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-(4-methoxy-2-methylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-(4-methoxy-3-methylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(2-cyanoethyl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{3-fluoro-4-[(cis-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{3-fluoro-4-[(4-hydroxy-4-methylcyclohexyl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[4-(2-hydroxy-1,1-dimethylethyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[4-(1-hydroxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[4-(1-methoxycyclobutyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2,6-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-methylsulfonyl)butanamide;(2R)-4-{4-[2-fluoro-4-(trifluoromethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(cyanomethyl)thio]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(cyanomethyl)thio]-2-methylphenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(1-cyanoethy)thio]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[2-methyl-4-(2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-4-{4-[6-(1-hydroxy-1-methylethyl)-2-naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{6-[(1S)-1-hydroxyethyl]-2-naphthyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-ethoxy-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(1-cyano-1-methylethyl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-{4-[4-(1-methyl-1H-imidazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1H-1,2,3-triazol-1-yl)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-4-[4-(4-{[(4R)-4,5-dihydroxypentyl]oxy}phenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(3,4-dihydroxybutoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[4-(1H-imidazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-{4-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-{4-[4-(3-methyl-1H-pyrazol-5-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-{4-[4-(5-methylisoxazol-3-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1H-1,2,4-triazol-1-yl)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-4-{4-[2-fluoro-4-(2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(4,5-dimethyl-2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyridin-2-ylphenyl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-2-methyl-4-{4-[4-(4-methylpyrimidin-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(2-methyl-2H-tetrazol-5-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(4-methyl-1H-1,2,3-triazol-1-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(5-methyl-1H-tetrazol-1-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(5-methyl-2H-tetrazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-4-[4-(4-isothiazol-4-ylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[6-(4-hydroxypiperidin-1-yl)-2-naphthyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(3,5-dimethyl-4H-1,2,4-triazol-4-yl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(3-methyl-4H-1,2,4-triazol-4-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;(2R)-4-{4-[4-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2-ethoxyquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2,4-dichlorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[4-(5-methoxypyrimidin-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[4-(1H-imidazol-1-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(1,3-oxazol-4-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-4-[4-(4-isopropoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(trifluoromethoxy)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-4-[4-(2-chloro-5-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2-fluoro-4-methoxyphenyl)-3-methyl-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-chloro-2-fluorophenyl)-3-methyl-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-fluorophenyl)-3-methyl-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-chlorophenyl)-3-methyl-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-(4-methoxyphenyl)-3-methyl-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-cyanophenyl)-3-methyl-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(difluoromethoxy)phenyl]-3-methyl-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyrimidin-4-ylphenyl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(1-oxido-2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyridin-4-ylphenyl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-4-[4-{4-[2-(2-methoxyethoxy)ethoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2-ethoxypyrimidin-5-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1,3-thiazol-4-yl)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1,3-thiazol-5-yl)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-4-{4-[4-(4-hydroxy-2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[3-(hydroxymethyl)isoxazol-5-yl]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[2-(dimethylamino)pyrimidin-5-yl]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-{4-[4-(2-methoxypyrimidin-5-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-(4-isoxazol-5-ylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-cyano-2-fluorophenyl)-3-methyl-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3-chloro-2-fluorophenyl)-3-methyl-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2,3-dichlorophenyl)-3-methyl-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(6-cyanopyridin-3-yl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(4,5-dimethyl-1H-1,2,3-triazol-1-yl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(1,2,4-oxadiazol-5-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-4-[6-(hydroxymethyl)-2′-oxo-3,4′-bipyridin-1′(2′H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1,2,4-thiadiazol-5-yl)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-4-[1′-(5-methylpyrimidin-2-yl)-2-oxo-1′,2′,3′,6′-tetrahydro-4,4′-bipyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1H-tetrazol-1-yl)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-4-{4-[4-(6-methylpyridin-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyrimidin-5-ylphenyl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyrimidin-2-yloxy)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-{4-[(5-propylpyrimidin-2-yl)oxy]phenyl}pyridin-1(2H)-yl]butanamide;(2R)-4-{4-[4-(2-cyanophenoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(3-cyanopyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(4-chloropyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyrazin-2-yloxy)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-4-[4-{4-[(5-chloropyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(3-cyano-4-methylpyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-[4-{4-[(4-methylpyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yloxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(5-chloropyrimidin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-[4-{4-[(3-methylpyrazin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-2-yloxy)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-4-{4-[4-(furo[3,2-c]pyridin-4-yloxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(3-cyano-6-methylpyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-{4-[(1-isopropyl-1H-tetrazol-5-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(3-chloropyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(3-cyano-4,6-dimethylpyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(2-cyanopyridin-3-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-[4-{4-[(5-methylpyrimidin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(quinolin-4-yloxy)phenyl]pyridin-1(2H)-yl}butanamide;(2R)-4-{4-[4-(1,3-benzothiazol-2-yloxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(3-cyano-4-methoxypyridin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-[4-{4-[(2-methylpyridin-4-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(5-fluoropyrimidin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-{4-[(4,6-dimethylpyrimidin-2-yl)oxy]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(1,2-benzisoxazol-3-yloxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2,3-dichloro-5-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2,3-dichloro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-pyridazin-3-ylphenyl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-4-[4-(4-isoxazol-4-ylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{4-[4-(4-methyl-2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}butanamide;(2R)-N-hydroxy-2-methyl-4-{4-[4-(6-methylpyridin-3-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-{4-[4-(5-methylpyrazin-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;(2R)-4-{4-[4-(5-chloropyrimidin-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3,5-difluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2S)-4-[4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-{4-[4-(5-ethylpyrimidin-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(tetrahydrofuran-2-ylmethoxy)phenyl]pyridin-1(2H)-yl}butanamide;trans-4-[(4-{1-[(3R)-4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}phenoxy)methyl]cyclohexyldihydrogen phosphate;(2R)-4-[4-(4-butylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-propylphenyl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-4-[4-(3-isopropylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-cyano-3-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-4-[4-(3-methoxy-2-methylphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(1-phenyl-1H-pyrazol-4-yl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-4-{4-[3-(2-methoxyethyl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(5-phenyl-1,3,4-thiadiazol-2-yl)pyridin-1(2H)-yl]butanamide;(2R)-4-[4-(4-cyano-2-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3-aminoisoquinolin-7-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2-phenyl-1,3-oxazol-5-yl)pyridin-1(2H)-yl]butanamide;(2R)-4-[4-{3-[(1-cyanoethyl)thio]phenyl}-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3-cyano-4-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-cyano-2-fluoro-5-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;methyl3-(4-{1-[(3R)-4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl]-2-oxo-1,2-dihydropyridin-4-yl}phenyl)propanoate;(2R)-4-[4-(3-cyano-4-ethoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-{4-[3-(difluoromethoxy)phenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(1-oxo-3,4-dihydro-1H-isochromen-7-yl)pyridin-1(2H)-yl]butanamide;(2R)-N-hydroxy-4-[4-(4-methoxyquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-4-[4-(4-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide;(2R)-4-[4-(3-aminoisoquinolin-6-yl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(3-oxo-1,3-dihydro-2-benzofuran-5-yl)pyridin-1(2H)-yl]butanamide;(2R)-4-{4-[4-(difluoromethoxy)-2,3-difluorophenyl]-2-oxopyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;and4-[4-(3-cyclopentylpropoxy)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;or a pharmaceutically acceptable salt thereof.
 2. A pharmaceuticalcomposition comprising a compound according to claim 1, or apharmaceutically acceptable salt thereof in admixture with at least onepharmaceutically acceptable excipient.
 3. A method of treating abacterial infection in a patient, the method comprising contacting thebacteria in the patient with a therapeutically effective amount of acompound according to claim 1, or a pharmaceutically acceptable saltthereof.
 4. The method according to claim 3 wherein the bacterialinfection is a Gram-negative bacterial infection.
 5. The methodaccording to claim 4 wherein the Gram-negative bacterial infection iscaused by a Gram-negative bacteria selected from the group consisting ofAcinetobacter baumannii, Acinetobacter spp., Citrobacter spp.,Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli,Klebsiella oxytoca, Klebsiella pneumoniae, Serratia marcescens,Stenotrophomonas maltophilia, and Pseudomonas aeruginosa.
 6. The methodaccording to claim 3 wherein the bacterial infection is selected fromthe group consisting of nosocomial pneumonia, urinary tract infection,bacteremia, sepsis, skin infection, soft-tissue infection,intraabdominal infection, lung infection, endocarditis, diabetic footinfection, osteomyelitis and central nervous system infection.
 7. Amethod of treating a bacterial infection in a patient, the methodcomprising administering a therapeutically effective amount of acompound according to claim 1, or a pharmaceutically acceptable saltthereof to a patient in need of treatment thereof.